Assembly/disassembly of drug conjugates using imide ligation - Mhidia, R.; Beziere, N.; Blanpain, A.; Pommery, N.; Melnyk, O. (Org. Lett., 2010)
A strategy is described that allows the easy assembly and controlled disassembly of drug conjugates. Imide ligation, that is, the reaction of a peptide thioacid with an azidoformate, is used for conjugate assembly. The imide bond participates also with an endopeptidase-triggered cyclization-based disassembly mechanism.
Mhidia, Reda Beziere, Nicolas Blanpain, Annick Pommery, Nicole Melnyk, Oleg Research Support, Non-U.S. Gov't United States Organic letters Org Lett. 2010 Sep 17;12(18):3982-5. doi: 10.1021/ol101049g.
The following values have no corresponding Zotero field: auth-address: UMR CNRS 8161, Universite de Lille Nord de France, IFR 142, Institut Pasteur de Lille, 1 rue du Pr Calmette 59021 Lille, France. number: 18 edition: 2010/08/24 accession-num: 20726571
Keywords: Amino Acid Sequence; Molecular Structure; Peptides/chemistry; Cyclization; Endopeptidases/metabolism; Imides/*chemistry/metabolism

Traceless ligation of cysteine peptides using selective deselenization - Metanis, N.; Keinan, E.; Dawson, P. E. (Angew. Chem. Int. Ed., 2010)
Metanis, Norman Keinan, Ehud Dawson, Philip E GM059380/GM/NIGMS NIH HHS/United States R01 GM059380-01/GM/NIGMS NIH HHS/United States R01 GM059380-02/GM/NIGMS NIH HHS/United States R01 GM059380-03/GM/NIGMS NIH HHS/United States R01 GM059380-04/GM/NIGMS NIH HHS/United States R01 GM059380-05/GM/NIGMS NIH HHS/United States R01 GM059380-06A2/GM/NIGMS NIH HHS/United States R01 GM059380-06A2S1/GM/NIGMS NIH HHS/United States R01 GM059380-07/GM/NIGMS NIH HHS/United States R01 GM059380-08/GM/NIGMS NIH HHS/United States R01 GM059380-09/GM/NIGMS NIH HHS/United States R01 GM059380-09S1/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Germany Angewandte Chemie (International ed. in English) Angew Chem Int Ed Engl. 2010 Sep 17;49(39):7049-53. doi: 10.1002/anie.201001900.
The following values have no corresponding Zotero field: auth-address: Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel. number: 39 edition: 2010/08/18 accession-num: 20715234
Keywords: Amino Acid Sequence; Peptides/*chemistry; Cysteine/*chemistry; Phosphines/chemistry; Alanine/chemistry; Selenocysteine/chemistry

Automated Fmoc-based solid-phase synthesis of peptide thioesters with self-purification effect and application in the construction of immobilized SH3 domains - Mende, F.; Beisswenger, M.; Seitz, O. (J. Am. Chem. Soc., 2010)
Peptide thioesters are important building blocks in the total synthesis of proteins and protein domains via fragment ligation. However, synthetic access of peptide thioesters still is a bottleneck of this powerful ligation chemistry. The commonly used methods for the Fmoc-based synthesis of peptide thioesters involve nonautomated solution steps that have to be performed after the solid-phase assembly of the peptide. Usually, HPLC purification is required. Herein, a method that enables crude peptides to be used in divergent native chemical ligations reactions is described. We present an Fmoc-based solid-phase synthesis of peptide thioesters with self-purification which facilitates access to these important building blocks, since the often cumbersome HPLC purification can be avoided. Fmoc-protected amino acids are coupled on a safety catch sulfonamide resin. The self-purifying effect is achieved through the combination of (a) N-terminal coupling of a cleavable cyclization linker and subsequent backbone-to-side chain cyclization, (b) activation of the sulfonamide linkage by alkylation, (c) thiolysis for the selective detachment of truncation products, and (d) TFA cleavage for the liberation of the desired peptide thioester in unprotected form. We have previously shown a method wherein cyclization was performed after carboxymethylation of the sulfonamide. However, the automation of this method was difficult and side reactions at methionine residues hampered the general applicability. The new design involves peptide synthesis on a modified carboxy-functionalized sulfonamide linker, a substantially milder activation of the sulfonamide bond and the use of monomethoxytrityl as well as 2-phenyl-isopropyl protecting groups. This approach solved the problems with methionine containing peptides and enabled the complete automation of the self-purifying synthesis of peptide thioesters. The study also addressed problems in the synthesis of difficult peptides. Aggregated truncation products can resist extraction and contaminate full-length thioesters obtained after TFA cleavage. It is shown that significant enhancements of the purity were achieved when mild acidic extractions were included in the wash protocols after thiolysis. The potential of the method was demonstrated in the parallel synthesis of 20-40 amino acid long peptide thioesters, which were obtained in excellent purities. The thioesters and cysteinyl peptides were used without purification in the assembly of immobilized SH3 protein domains of SHO1 in yeast. A cysteine scan by native chemical ligation suggested single amino acid to cysteine substitutions that (a) confer useful ligation yields, (b) support correct folding, and (c) sustain the function of the folded protein domain. The chemical synthesis of the SH3-domain of SHO1 succeeded in highest yields when cysteine placements at positions S23, F24, and E36 were avoided. The synthetic SH3 mutants were examined in a binding assay, which indicated that N27C, L30C, and D34C mutations provide functional SH3-domain.
1520-5126 (Electronic) 0002-7863 (Linking) Journal Article Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Institut fur Chemie, Humboldt-Universitat zu Berlin, Brook-Taylor-Strasse 2, D-12489 Berlin, Germany. number: 32 accession-num: 20662535
Keywords: Amino Acid Sequence; Cysteine/chemistry; Molecular Sequence Data; Sulfhydryl Compounds/*chemistry; Protein Folding; Peptides/*chemical synthesis/*chemistry; Ligands; *src Homology Domains; Automation; Fluorenes/*chemistry; Immobilized Proteins/*chemistry; Membrane Proteins/chemistry; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins/chemistry

Total chemical synthesis of human proinsulin - Luisier, S.; Avital-Shmilovici, M.; Weiss, M. A.; Kent, S. B. H. (Chem. Commun., 2010)
A convergent synthetic strategy based on modern chemical ligation methods was used to make human proinsulin. The synthetic protein was characterized by LCMS, CD spectroscopy, and by 1D- and 2D-NMR spectroscopy. Synthetic human proinsulin had full biochemical activity in a receptor-binding assay.
1364-548X (Electronic) 1359-7345 (Linking) Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois 60637, USA. number: 43 accession-num: 20877850
Keywords: Amino Acid Sequence; Humans; Stereoisomerism; Molecular Sequence Data; Circular Dichroism; Proinsulin/*chemical synthesis/chemistry

A tris (2-carboxyethyl) phosphine (TCEP) related cleavage on cysteine-containing proteins - Liu, P.; O'Mara, B. W.; Warrack, B. M.; Wu, W.; Huang, Y.; Zhang, Y.; Zhao, R.; Lin, M.; Ackerman, M. S.; Hocknell, P. K.; Chen, G.; Tao, L.; et al. (J. Am. Soc. Mass Spectrom., 2010)
Introduced in the late 1980s as a reducing reagent, Tris (2-carboxyethyl) phosphine (TCEP) has now become one of the most widely used protein reductants. To date, only a few studies on its side reactions have been published. We report the observation of a side reaction that cleaves protein backbones under mild conditions by fracturing the cysteine residues, thus generating heterogeneous peptides containing different moieties from the fractured cysteine. The peptide products were analyzed by high performance liquid chromatography and tandem mass spectrometry (LC/MS/MS). Peptides with a primary amine and a carboxylic acid as termini were observed, and others were found to contain amidated or formamidated carboxy termini, or formylated or glyoxylic amino termini. Formamidation of the carboxy terminus and the formation of glyoxylic amino terminus were unexpected reactions since both involve breaking of carbon-carbon bonds in cysteine.
Journal Article United States
The following values have no corresponding Zotero field: auth-address: Department of Biologics Product and Process Development, Bristol-Myers Squibb Technical Operations, Princeton, New Jersey 08543, USA. alt-title: Journal of the American Society for Mass Spectrometry number: 5 accession-num: 20189823
Keywords: Hydrogen-Ion Concentration; Proteins/*chemistry/metabolism; Cysteine/*chemistry/metabolism; Chromatography, High Pressure Liquid/*methods; Peptide Fragments/*chemistry/metabolism; Phosphines/*chemistry; Tandem Mass Spectrometry/*methods

Adding new chemistries to the genetic code - Liu, C. C.; Schultz, P. G. (Annu. Rev. Biochem., 2010)
The development of new orthogonal aminoacyl-tRNA synthetase/tRNA pairs has led to the addition of approximately 70 unnatural amino acids (UAAs) to the genetic codes of Escherichia coli, yeast, and mammalian cells. These UAAs represent a wide range of structures and functions not found in the canonical 20 amino acids and thus provide new opportunities to generate proteins with enhanced or novel properties and probes of protein structure and function.
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review United States
The following values have no corresponding Zotero field: auth-address: The Scripps Research Institute, La Jolla, California 92037, USA. ccliu@berkeley.edu alt-title: Annual review of biochemistry accession-num: 20307192
Keywords: Animals; Amino Acids/*chemistry; *Genetic Code; *Protein Engineering; Amino Acyl-tRNA Synthetases/chemistry; Escherichia coli/chemistry/genetics/metabolism; RNA, Transfer/chemistry; Saccharomyces cerevisiae/chemistry/genetics/metabolism

Macrolactonization of peptide thioesters catalyzed by imidazole and its application in the synthesis of Kahalalide B and analogues - Li, Yangmei; Giulionatti, Marc; Houghten, Richard A. (Org. Lett., 2010)
doi: 10.1021/ol100596p 1523-7060 doi: 10.1021/ol100596p
The following values have no corresponding Zotero field: number: 10 publisher: American Chemical Society

The chemical ligation of selectively S-acylated cysteine peptides to form native peptides via 5-, 11- and 14-membered cyclic transition states - Katritzky, A. R.; Abo-Dya, N. E.; Tala, S. R.; Abdel-Samii, Z. K. (Org. Biomol. Chem., 2010)
Cysteine and C-terminal cysteine peptides are selectively S-acylated at 0-20 degrees C by N-(Pg-alpha-aminoacyl)benzotriazoles to give N-Pg-S-acyl-isodi-, -isotri-, and -isotetra-peptides isolated in good yields. N-Fmoc-S-acyl-isopeptides are Fmoc deprotected to afford free S-acyl-isopeptides isolated in high yields. S-Acyl-isodi-, S-acyl-isotetra-, and S-acyl-isopentapeptides undergo chemical ligation; migration of the cysteine S-acyl groups to the N-terminal amino acids via 5-, 11-, and 14-membered transition states giving the corresponding native di-, tetra-, and penta-peptides. By contrast, the Sacyl-isotripeptide prefers intermolecular acylation from one molecule to another over an 8-membered intramolecular transition state. The developed methodology allows convenient isolation of stable, unprotected S-acyl cysteine peptides including the first isolation of S-acyl-isopeptides, which should facilitate the investigation of ligation by physical organic chemistry techniques.
Journal Article England
The following values have no corresponding Zotero field: auth-address: Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, USA. katritzky@chem.ufl.edu alt-title: Organic & biomolecular chemistry number: 10 accession-num: 20372743
Keywords: Cysteine/*chemistry; Acylation; Substrate Specificity; Triazoles/chemistry; Sulfur/*chemistry; Peptides, Cyclic/*chemistry; Hydroxides/chemistry; Microwaves

Peptide and protein thioester synthesis via N->S acyl transfer - Kang, J.; Macmillan, D. (Org. Biomol. Chem., 2010)
Peptide and protein thioesters are playing an increasingly prominent role in the chemical toolbox for protein assembly and modification through Native Chemical Ligation (NCL). In this Emerging Area we highlight recent developments in a somewhat surprising route to thioesters: selective disruption of amides, the more stable carboxylic acid derivatives.
1477-0539 (Electronic) 1477-0520 (Linking) Journal Article Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, University College London, 20 Gordon Street, London, UK WC1H 0AJ. number: 9 accession-num: 20401371
Keywords: Stereoisomerism; Peptides/*chemistry; Molecular Structure; Proteins/*chemistry; Sulfhydryl Compounds/*chemical synthesis/chemistry; Amides/chemistry

Ionization constants of acids and bases - Jencks, W. P.; Regenstein, J. (Handbook of Biochemistry and Molecular Biology, 2010)
Keywords: #nosource

Total synthesis of the large non-ribosomal peptide polytheonamide B - Inoue, M.; Shinohara, N.; Tanabe, S.; Takahashi, T.; Okura, K.; Itoh, H.; Mizoguchi, Y.; Iida, M.; Lee, N.; Matsuoka, S. (Nat. Chem., 2010)
Polytheonamide B is by far the largest non-ribosomal peptide known at present, and displays extraordinary cytotoxicity (EC(50) = 68 pg ml(-1), mouse leukaemia P388 cells). Its 48 amino-acid residues include a variety of non-proteinogenic d- and l-amino acids, and the absolute stereochemistry of these amino acids alternate in sequence. These structural features induce the formation of a stable beta-strand-type structure, giving rise to an overall tubular structure over 30 A in length. In a biological setting, this fold is believed to transport cations across the lipid bilayer through a pore, thereby acting as an ion channel. Here, we report the first chemical construction of polytheonamide B. Our synthesis relies on the combination of four key stages: syntheses of non-proteinogenic amino acids, a solid-phase assembly of four fragments of polytheonamide B, silver-mediated connection of the fragments and, finally, global deprotection. The synthetic material now available will allow studies of the relationships between its conformational properties, channel functions and cytotoxicity.
Inoue, Masayuki Shinohara, Naoki Tanabe, Shintaro Takahashi, Tomoaki Okura, Ken Itoh, Hiroaki Mizoguchi, Yuki Iida, Maiko Lee, Nayoung Matsuoka, Shigeru England Nat Chem. 2010 Apr;2(4):280-5. doi: 10.1038/nchem.554. Epub 2010 Feb 21.
The following values have no corresponding Zotero field: auth-address: The University of Tokyo, Tokyo 113-0033, Japan. inoue@mol.f.u-tokyo.ac.jp alt-title: Nature chemistry number: 4 edition: 2010/12/03 accession-num: 21124508
Keywords: Animals; Stereoisomerism; Fluorenes/chemistry; Mice; Cell Line, Tumor; Antineoplastic Agents/chemical synthesis/chemistry/pharmacology; Peptide Fragments/chemistry; Proteins/*chemical synthesis/*chemistry/pharmacology; Safrole/analogs & derivatives/chemistry

The mercaptomethyl group facilitates an efficient one-pot ligation at Xaa-Ser/Thr for (glyco)peptide synthesis - Hojo, H.; Ozawa, C.; Katayama, H.; Ueki, A.; Nakahara, Y.; Nakahara, Y. (Angew. Chem. Int. Ed., 2010)
1521-3773 (Electronic) 1433-7851 (Linking) Journal Article Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Department of Applied Biochemistry, Institute of Glycoscience, Tokai University, 1117 Kitakaname, Hiratsuka, Kanagawa 259-1292, Japan. hojo@keyaki.cc.u-tokai.ac.jp number: 31 accession-num: 20803702

Synthesis of two new thioesters bearing ferrocene: Vibrational characterization and ab initio calculations. X-ray crystal structure of S-(2-methoxyphenyl)ferrocenecarbothioate - Henao Castaneda, Isabel C.; Della Védova, Carlos O.; Piro, Oscar E.; Metzler-Nolte, Nils; Jios, Jorge L. (Polyhedron, 2010)
Structural and conformational properties of S-benzyl ferrocenecarbothioate (I) and S-(2-methoxyphenyl) ferrocenecarbothioate (II) are analyzed using data obtained from X-ray diffraction, vibrational data and theoretical calculations. According to chemical quantum calculations, the synperiplanar and antiperiplanar forms are found as the first and second more stable conformations, respectively, for the title compounds. The geometric parameters and normal modes of vibration were calculated using a density functional theory method (B3LYP) and the 6-31+Gâˆ—âˆ— basis set for all atoms except for iron. For this atom the calculations were carried out with the Lanl2dz basis set. The calculated parameters are in good agreement with the corresponding X-ray diffraction values. The combined experimental and theoretical approach allows a consistent assignment for most of the fundamental modes.
0277-5387
The following values have no corresponding Zotero field: number: 2
Keywords: Conformation analysis; Density functional calculations; Ferrocenecarbothioates; Metallocenes; Vibrational analysis; X-ray single crystal analysis

Toward the total chemical synthesis of the cancer protein NY-ESO-1 - Harris, Paul W. R.; Brimble, Margaret A. (Pept. Sci., 2010)
During the course of developing a synthetic route for the cancer protein NY-ESO-1 using native chemical ligation, a number of the required thioester polypeptide fragments were unable to be synthesized effectively using Boc solid phase peptide synthesis. Modification of the SPPS protocols to include an arginine tag at the C terminus linked via the thioester resulted in a better purity profile and enhanced solubility, facilitating purification by HPLC. During preparation of another reactive partner for ligation that contained an internal Cys(Acm) residue by Fmoc SPPS, extensive loss of the Acm group occurred during cleavage from the resin while substitution with Cys(tBu) resulted in no loss of protecting group. It was shown that native chemical ligation of N-terminal cysteine peptide 155–180 containing the Cys(tBu) residue with thioester 140–154 was slow, incomplete and led to extensive HPLC column fouling. Subsequent incorporation of a C-terminal arginine tag into the N-terminal NY-ESO-1 155-180 fragment joined by a base labile 4-hydroxymethylbenzoic acid (HMBA) linker facilitated rapid quantitative ligation. The HMBA linker was demonstrated to be stable to the conditions required for native chemical ligation, subsequent transformations and final purification. Importantly it was effectively removed at pH = 10. © 2010 Wiley Periodicals, Inc.Biopolymers (Pept Sci) 94: 542–550, 2010.
1097-0282
The following values have no corresponding Zotero field: number: 4 publisher: Wiley Subscription Services, Inc., A Wiley Company
Keywords: native chemical ligation; arginine tag; cancer protein; HMBA linker; solid phase peptide synthesis

Protein synthesis assisted by native chemical ligation at leucine - Harpaz, Z.; Siman, P.; Kumar, K. S.; Brik, A. (ChemBioChem, 2010)
1439-7633 (Electronic) 1439-4227 (Linking) Journal Article Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel. number: 9 accession-num: 20437446

Protecting group variations of delta-mercaptolysine useful in chemical ubiquitylation - Haj-Yahya, M.; Ajish Kumar, K. S.; Erlich, L. A.; Brik, A. (Biopolymers, 2010)
The high efficiency and chemoselectivity of peptide ubiquitylation that is achieved using the delta-mercaptolysine prompted us to expand the scope of this residue in various ligation schemes. In this report, we demonstrate the synthesis of five analogues of this important amino acid bearing a variety of protecting groups, which is essential in sequential peptide ligation and ubiquitylation. The key-step in the synthesis is the nucleophilic 1,4-addition of a variety of thiols on a nitro olefin scaffold.
Journal Article Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel. alt-title: Biopolymers number: 4 accession-num: 20564006
Keywords: Animals; Humans; *Ubiquitination; Peptides/*chemical synthesis/*chemistry; Amino Acids/*chemical synthesis/*chemistry

Dynamic cyclic thiodepsipeptide libraries from thiol-thioester exchange - Ghosh, Soumyadip; Ingerman, Lindsey A.; Frye, Aaron G.; Lee, Stephen J.; Gagné, Michel R.; Waters, Marcey L. (Org. Lett., 2010)
Thiol−thioester exchange was found to readily generate libraries of cyclic thiodepsipeptides under thermodynamic control, which will enable their use in a variety of dynamic combinatorial chemistry assays. The kinetic determinants of macrocycle formation and the role of amino acid structure on the reaction dynamics are discussed.
The following values have no corresponding Zotero field: number: 8 publisher: American Chemical Society

N-methylcysteine-mediated total chemical synthesis of ubiquitin thioester - Erlich, L. A.; Kumar, K. S.; Haj-Yahya, M.; Dawson, P. E.; Brik, A. (Org. Biomol. Chem., 2010)
Ubiquitin thioester is a key intermediate in the ubiquitylation of proteins and is formed enzymatically through the activation of alpha-COOH of ubiquitin in an ATP dependent manner using the E1 enzyme. The current methods used for the preparation of ubiquitin thioester rely on either the enzymatic machinery or on expressed protein ligation technology. In this article, we report a new chemical strategy, combining native chemical ligation and N-methylcysteine containing peptides, to chemically prepare ubiquitin thioester for the first time. The N-methylcysteine is utilized as an N-->S acyl transfer device, and in its protected form serves as a latent thioester functionality. This enabled us to trigger the formation of ubiquitin thioester subsequent to the assembly of the ubiquitin polypeptide via native chemical ligation. The synthetic ubiquitin thioester showed a similar behavior in peptide ubiquitylation to the one obtained via expression. This approach should allow for higher flexibility in the chemical manipulation of ubiquitin thioester in a wide variety of ubiquitylated peptides and proteins for structural and biochemical analysis and for the synthesis of ubiquitin chains.
1477-0539 (Electronic) 1477-0520 (Linking) Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Ben Gurion University, Beer Sheva, Israel 84105. number: 10 accession-num: 20448897
Keywords: Amino Acid Sequence; Molecular Sequence Data; Chromatography, High Pressure Liquid; Cysteine/*analogs & derivatives/chemistry; Dendrimers/chemistry; Glycopeptides/chemical synthesis/chemistry; Ubiquitin/*chemical synthesis/*chemistry; Ubiquitins/*chemical synthesis/*chemistry

Chemical synthesis of ubiquitin, ubiquitin-based probes, and diubiquitin - El Oualid, F.; Merkx, R.; Ekkebus, R.; Hameed, D. S.; Smit, J. J.; de Jong, A.; Hilkmann, H.; Sixma, T. K.; Ovaa, H. (Angew. Chem. Int. Ed., 2010)
El Oualid, Farid Merkx, Remco Ekkebus, Reggy Hameed, Dharjath S Smit, Judith J de Jong, Annemieke Hilkmann, Henk Sixma, Titia K Ovaa, Huib Research Support, Non-U.S. Gov't Germany Angewandte Chemie (International ed. in English) Angew Chem Int Ed Engl. 2010 Dec 27;49(52):10149-53. doi: 10.1002/anie.201005995.
The following values have no corresponding Zotero field: auth-address: Division of Cell Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. number: 52 edition: 2010/12/01 accession-num: 21117055
Keywords: Amino Acid Sequence; Mutation; Molecular Sequence Data; Protein Folding; Peptides/*chemical synthesis/chemistry/genetics; Ubiquitin/*chemical synthesis/chemistry/genetics

Synthesis of defined ubiquitin dimers - Eger, S.; Scheffner, M.; Marx, A.; Rubini, M. (J. Am. Chem. Soc., 2010)
Many proteins are post-translationally modified by the attachment of poly-ubiquitin (Ub) chains. Notably, the biological function of the attached Ub chain depends on the specific lysine residue used for conjugate formation. Here, we report an easy and efficient method to synthesize site-specifically linked Ub dimers by click reaction between two artificial amino acids. In fact, we were able to synthesize all seven naturally occurring Ub connectivities, providing the first example of a method that gives access to all Ub dimers. Furthermore, these synthetic Ub dimers are recognized by the natural ubiquitination machinery and are proteolytically stable, making them optimal candidates to further investigate the function of differently linked Ub chains.
Eger, Silvia Scheffner, Martin Marx, Andreas Rubini, Marina Research Support, Non-U.S. Gov't United States Journal of the American Chemical Society J Am Chem Soc. 2010 Nov 24;132(46):16337-9. doi: 10.1021/ja1072838. Epub 2010 Oct 29.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Konstanz Research School Chemical Biology, University of Konstanz, 78457 Konstanz, Germany. number: 46 edition: 2010/11/03 accession-num: 21033666
Keywords: Amino Acid Sequence; Models, Molecular; Molecular Structure; Molecular Sequence Data; Dimerization; Ubiquitin/*chemical synthesis/chemistry

Matrix photochemistry at low temperatures and spectroscopic properties of gamma-butyrothiolactone - Dugarte, N. Y.; Erben, M. F.; Romano, R. M.; Ge, M. F.; Li, Y.; Della Védova, Carlos O. (J. Phys. Chem. A, 2010)
The five-membered heterocyclic gamma-butyrothiolactone was isolated in a low-temperature, inert Ar matrix, and the UV-visible (200 <or= lambda <or= 800 nm)-induced photochemistry was studied. On the basis of the IR spectra, the formation of ethylketene (CH(3)CH(2)CH=C=O) was identified as the main channel of photodecomposition. The valence electronic structure was investigated by He(I) photoelectron spectroscopy assisted by quantum chemical calculations at the outer valence Green's function/6-311++G(d,p) level of theory. The first three bands at 9.54, 9.69, and 11.89 eV are assigned to the n(S), n(O), and pi(C=O) orbitals, respectively, denoting the importance of the -SC(O)- group in the outermost electronic properties. The conventional ring strain energy was determined to be 3.8 kcal mol(-1) at the G2MP2 level of calculation within the hyperhomodesmotic model.
Journal Article Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: CEQUINOR (UNLP-CONICET, CCT La Plata), Departamento de Quimica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, C.C. 962 (1900), La Plata, Republica Argentina. alt-title: The journal of physical chemistry number: 35 accession-num: 20718471
Keywords: Molecular Structure; Molecular Dynamics Simulation; *Temperature; Lactones/*chemistry; Photochemistry; Quantum Theory; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet

Molecular and electronic structure of delta-valerothiolactone - Dugarte, N. Y.; Erben, M. F.; Boese, R.; Ge, M. F.; Yao, L.; Della Védova, Carlos O. (J. Phys. Chem. A, 2010)
The crystal structure of the six-member heterocyclic delta-valerothiolactone (1-thiocycloalkan-2-one) compound has been determined by X-ray diffraction at low temperature, revealing that its skeleton adopts a half-chair conformation. The conformation around the thioester group is almost planar with an anti orientation of the C=O double bond with respect the S-C single bond [C(2)-S(1)-C(6)-O(1) = 176.26(8) degrees ]. The skeletal parameters, especially valence angles [ angleC5-C6-S = 121.19(6) degrees , angleO=C6-C5 = 122.25(8) degrees , angleC6-S-C2 = 106.80(4) degrees ], differ from those typically found in acyclic thioester compounds, symptomatic of the presence of strain effects. The conventional ring strain energy was determined to be 7.5 kcal/mol at the MP2/6-311++G(d,p) level of calculation within the hyperhomodesmotic model approximation. Moreover, the valence electronic structure was investigated by HeI photoelectron spectroscopy assisted by quantum chemical calculations at the OVGF/6-311++G(d,p) level of theory. The first three bands at 9.35, 9.50, and 11.53 eV denote ionizations related with the n(S), n(O), and pi(C=O) orbitals, respectively, demonstrating the importance of the -SC(O)- group in the outermost electronic properties.
Journal Article Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: CEQUINOR (UNLP-CONICET, CCT La Plata), Departamento de Quimica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, C.C. 962 (1900), La Plata, Republica Argentina. alt-title: The journal of physical chemistry number: 47 accession-num: 21049894
Keywords: Models, Molecular; Temperature; Molecular Conformation; Molecular Structure; Crystallography, X-Ray/methods; Electrons; Models, Chemical; Computer Simulation; Lactones/*chemistry; Quantum Theory; Carbon/chemistry; Oxygen/chemistry; Pyrones/*chemistry; Spectrophotometry, Infrared/methods; X-Ray Diffraction

Readily Accessible Bicyclononynes for Bioorthogonal Labeling and Three-Dimensional Imaging of Living Cells - Dommerholt, Jan; Schmidt, Samuel; Temming, Rinske; Hendriks, Linda J. A.; Rutjes, Floris P. J. T.; van Hest, Jan C. M.; Lefeber, Dirk J.; Friedl, Peter; van Delft, Floris L. (Angew. Chem. Int. Ed., 2010)
The following values have no corresponding Zotero field: number: 49 publisher: WILEY-VCH Verlag
Keywords: protein modification; cycloadditions; cycloalkynes; imaging; kinetics

Native chemical ligation of hydrophobic peptides in organic solvents - Dittmann, M.; Sauermann, J.; Seidel, R.; Zimmermann, W.; Engelhard, M. (J. Pept. Sci., 2010)
The application of chemistry to hydrophobic peptides and membrane-spanning helices is hampered by the fact that they are only poorly soluble in aqueous buffers and that they have a tendency for aggregation. These properties lead to difficulties when purifying them after chemical synthesis and particularly interfere with native chemical ligation. Here, we describe native chemical ligation of model peptides in the organic solvent dimethylformamide (DMF) under anhydrous conditions. Best results concerning yields and complete solubility are obtained if thiophenole is used in the presence of LiCl. These conditions might be applicable also for the ligation of transmembrane helices.
Journal Article Research Support, Non-U.S. Gov't England an official publication of the European Peptide Society
The following values have no corresponding Zotero field: auth-address: Max Planck Institute of Molecular Physiology, Dortmund, Germany. number: 10 accession-num: 20814908
Keywords: Peptides/*chemistry; Water/chemistry; Dimethylformamide/chemistry; Solvents/*chemistry

Native chemical ligation in dimethylformamide can be performed chemoselectively without racemization - Dittmann, M.; Sadek, M.; Seidel, R.; Engelhard, M. (J. Pept. Sci., 2010)
Native chemical ligation of unprotected peptides in organic solvents has been previously reported as a fast, efficient, and suitable method for coupling of hydrophobic peptides. However, it has not been determined whether the reaction can be carried out without possible side reactions or racemization. Here, we present a study on the chemoselectivity of this method by model reactions designed to test the reactivity of Arg and Lys side chains as well as that of alpha-amino groups. A possible racemization of the C-terminal amino acid of the N-terminal peptide was also investigated. The results show that ligation in organic solvents can be conducted chemoselectively without side reactions with other nucleophilic groups. Furthermore, no racemization of the C-terminal amino acid was observed if both educts were added simultaneously. Thus, native chemical ligation can be performed either in aqueous buffer systems or in organic solvents paving the way for the synthesis of larger hydrophobic peptides and/or membrane proteins.
Journal Article Research Support, Non-U.S. Gov't England an official publication of the European Peptide Society
The following values have no corresponding Zotero field: auth-address: Max Planck Institute of Molecular Physiology, Otto Hahn Str. 11, 44227, Dortmund, Germany. number: 5 accession-num: 22431434
Keywords: Stereoisomerism; Peptides/*chemical synthesis/*chemistry; Solvents/*chemistry; Dimethylformamide/*chemistry; Hydrophobic and Hydrophilic Interactions

Native chemical ligation in the synthesis of internally modified oligonucleotide-peptide conjugates - Diezmann, F.; Eberhard, H.; Seitz, O. (Biopolymers, 2010)
Peptide-oligonucleotide conjugates have frequently been synthesized to improve cellular delivery of antisense or antigene compounds, to allow the immobilization of peptide and protein conjugates on DNA arrays, or to decorate nucleic acid architectures with peptide functions. In such applications, the site of conjugation is of little importance, and peptides have predominantly been appended to one of the terminal ends of the oligonucleotide by using an oxime-, thioether-, or disulfide-linkage or native chemical ligation. We, herein, demonstrate the first coupling of peptides to sequence internal sites. This attachment mode provides better control of the spatial arrangement of peptides presented by self-assembled nucleic acid scaffolds. Internal modification requires special phosphoramidite building blocks that can be used in automated DNA synthesis. For this purpose, Fmoc/StBu-protected cysteine was attached via an aminopropargyl linker to the C5-position of uridine. The rigid triple bond conferred a high reactivity in native chemical ligation reactions of 5-6mer peptide thioesters with up to 15 nucleotides long oligonucleotides. The desired peptide-oligonucleotide conjugates were obtained in high yields after purification. UV melt experiments revealed that the peptide modification does not hamper nucleic acid hybridization. This finding marked an important step in our research program devoted to studies of multivalent presentation of peptides via modular assembly of nucleic acid complexes.
Journal Article Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: Institute of Chemistry, Humboldt-University of Berlin, Brook-Taylor-Str. 2, 12489 Berlin, Germany. alt-title: Biopolymers number: 4 accession-num: 20593471
Keywords: Peptides/*chemical synthesis/chemistry; Oligonucleotide Array Sequence Analysis/methods; Oligonucleotides/*chemical synthesis/chemistry

Energetics of the lighter chalcogen analogues of carboxylic acid esters - Deakyne, Carol A.; Ludden, Alicia K.; Roux, Maria Victoria; Notario, Rafael; Demchenko, Alexei V.; Chickos, James S.; Liebman, Joel F. (J. Phys. Chem. B, 2010)
doi: 10.1021/jp107208q 1520-6106 doi: 10.1021/jp107208q
The following values have no corresponding Zotero field: number: 49 publisher: American Chemical Society

Modulation of an n-->pi* interaction with alpha-fluoro groups - Choudhary, A.; Fry, C. G.; Raines, R. T. (ARKIVOC, 2010)
Noncovalent interactions play an essential role in biological and chemical processes. In the main chain of common protein secondary structures, the lone pair (n) of a carbonyl oxygen is delocalized into the antibonding orbital (pi*) of the subsequent carbonyl group. Herein, experimental and computational data reveal that this n-->pi* interaction can be attenuated by the inductive electron withdrawal of one or two alpha-fluoro groups in the donor. The steric effect of three alpha-fluoro groups, however, overcomes the inductive withdrawal. These data evoke a means to modulate the n-->pi* interaction in peptides, proteins, and other systems.
Choudhary, Amit Fry, Charles G Raines, Ronald T R01 AR044276-15/AR/NIAMS NIH HHS/United States Journal article ARKIVOC : free online journal of organic chemistry / Arkat-USA, Inc ARKIVOC. 2010 Jul 8;2010:251-262.
The following values have no corresponding Zotero field: edition: 2011/06/07 accession-num: 21643549

A program for ligation at threonine sites: application to the controlled total synthesis of glycopeptides - Chen, Jin; Wang, Ping; Zhu, Jianglong; Wan, Qian; Danishefsky, Samuel J. (Tetrahedron, 2010)
A method by which to accomplish formal threonine ligation has been developed. The method accomplishes ligations of two peptide domains. We have also demonstrated the ability to successfully ligate two independent glycopeptide domains.
0040-4020
The following values have no corresponding Zotero field: number: 13

Chemical approaches for studying histone modifications - Chatterjee, C.; Muir, T. W. (J. Biol. Chem., 2010)
Histones form the protein core around which genomic DNA is wrapped in eukaryotic chromatin. Numerous genetic studies have established that the structure and transcriptional state of chromatin are closely related to histone post-translational modifications. Further elucidation of the precise mechanistic roles for individual histone modifications requires the ability to isolate and study homogeneously modified histones. However, the highly heterogeneous nature of histone modifications in vivo poses a significant challenge for such studies. Chemical tools that have enabled biochemical and biophysical studies of site-specifically modified histones are the focus of this minireview.
1083-351X (Electronic) 0021-9258 (Linking) Journal Article Review
The following values have no corresponding Zotero field: auth-address: Laboratory of Synthetic Protein Chemistry, The Rockefeller University, New York, New York 10065, USA. number: 15 accession-num: 20147749
Keywords: Amino Acid Sequence; Animals; Humans; Molecular Conformation; Molecular Sequence Data; Histones/*chemistry; Peptides/chemistry; Models, Biological; Models, Chemical; Protein Processing, Post-Translational; Biotinylation; Biochemistry/methods; Biophysics/methods; Chromatin/chemistry; Nucleosomes/chemistry

Disulfide-directed histone ubiquitylation reveals plasticity in hDot1L activation - Chatterjee, C.; McGinty, R. K.; Fierz, B.; Muir, T. W. (Nat. Chem. Biol., 2010)
We have developed a readily accessible disulfide-directed methodology for the site-specific modification of histones by ubiquitin and ubiquitin-like proteins. The disulfide-linked analog of mono-ubiquitylated H2B stimulated the H3K79 methyltransferase activity of hDot1L to a similar extent as the native isopeptide linkage. This permitted structure-activity studies of ubiquitylated mononucleosomes that revealed plasticity in the mechanism of hDot1L stimulation and identified surfaces of ubiquitin important for activation.
Chatterjee, Champak McGinty, Robert K Fierz, Beat Muir, Tom W Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Nature chemical biology Nat Chem Biol. 2010 Apr;6(4):267-9. doi: 10.1038/nchembio.315. Epub 2010 Mar 7.
The following values have no corresponding Zotero field: auth-address: Laboratory of Synthetic Protein Chemistry, The Rockefeller University, New York, New York, USA. number: 4 edition: 2010/03/09 accession-num: 20208522
Keywords: Humans; Structure-Activity Relationship; Ubiquitination; Histones/*metabolism; Disulfides/*metabolism; Methyltransferases/*metabolism; Ubiquitin/metabolism; Ubiquitins/metabolism

n->p* interactions in proteins - Bartlett, G. J.; Choudhary, A.; Raines, R. T.; Woolfson, D. N. (Nat. Chem. Biol., 2010)
Hydrogen bonds between backbone amides are common in folded proteins. Here, we show that an intimate interaction between backbone amides also arises from the delocalization of a lone pair of electrons (n) from an oxygen atom to the antibonding orbital (pi*) of the subsequent carbonyl group. Natural bond orbital analysis predicted significant n-->pi* interactions in certain regions of the Ramachandran plot. These predictions were validated by a statistical analysis of a large, non-redundant subset of protein structures determined to high resolution. The correlation between these two independent studies is striking. Moreover, the n-->pi* interactions are abundant and especially prevalent in common secondary structures such as alpha-, 3(10)- and polyproline II helices and twisted beta-sheets. In addition to their evident effects on protein structure and stability, n-->pi* interactions could have important roles in protein folding and function, and merit inclusion in computational force fields.
Bartlett, Gail J Choudhary, Amit Raines, Ronald T Woolfson, Derek N D003016/Biotechnology and Biological Sciences Research Council/United Kingdom R01 AR044276/AR/NIAMS NIH HHS/United States R01 AR044276-15/AR/NIAMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Nature chemical biology Nat Chem Biol. 2010 Aug;6(8):615-20. doi: 10.1038/nchembio.406. Epub 2010 Jul 11.
The following values have no corresponding Zotero field: auth-address: School of Chemistry, University of Bristol, Bristol, United Kingdom. number: 8 edition: 2010/07/14 accession-num: 20622857
Keywords: Computational Biology; Models, Molecular; Proteins/*chemistry; Crystallography, X-Ray; Protein Structure, Secondary; Dipeptides/chemistry; *Hydrogen Bonding; *Protein Conformation; Databases, Nucleic Acid

Determination of the X-ray structure of the snake venom protein omwaprin by total chemical synthesis and racemic protein crystallography - Banigan, J. R.; Mandal, K.; Sawaya, M. R.; Thammavongsa, V.; Hendrickx, A. P.; Schneewind, O.; Yeates, T. O.; Kent, S. B. H. (Protein Sci, 2010)
The 50-residue snake venom protein L-omwaprin and its enantiomer D-omwaprin were prepared by total chemical synthesis. Radial diffusion assays were performed against Bacillus megaterium and Bacillus anthracis; both L- and D-omwaprin showed antibacterial activity against B. megaterium. The native protein enantiomer, made of L-amino acids, failed to crystallize readily. However, when a racemic mixture containing equal amounts of L- and D-omwaprin was used, diffraction quality crystals were obtained. The racemic protein sample crystallized in the centrosymmetric space group P2(1)/c and its structure was determined at atomic resolution (1.33 A) by a combination of Patterson and direct methods based on the strong scattering from the sulfur atoms in the eight cysteine residues per protein. Racemic crystallography once again proved to be a valuable method for obtaining crystals of recalcitrant proteins and for determining high-resolution X-ray structures by direct methods.
5R01 GM075993/GM/NIGMS NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. United States a publication of the Protein Society
The following values have no corresponding Zotero field: auth-address: Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois, USA. number: 10 accession-num: 20669184
Keywords: Amino Acid Sequence; Animals; Models, Molecular; Protein Conformation; Stereoisomerism; Molecular Sequence Data; Chromatography, High Pressure Liquid; Mass Spectrometry; Circular Dichroism; Crystallography, X-Ray; Models, Chemical; Antimicrobial Cationic Peptides/*chemical synthesis/*chemistry/pharmacology; Bacillus megaterium/drug effects/growth & development/ultrastructure; Elapid Venoms/*chemical synthesis/*chemistry/pharmacology; Microscopy, Electron, Scanning

The effects of histone H4 tail acetylations on cation-induced chromatin folding and self-association - Allahverdi, A.; Yang, R.; Korolev, N.; Fan, Y.; Davey, C. A.; Liu, C. F.; Nordenskiold, L. (Nucleic Acids Res., 2010)
Understanding the molecular mechanisms behind regulation of chromatin folding through covalent modifications of the histone N-terminal tails is hampered by a lack of accessible chromatin containing precisely modified histones. We study the internal folding and intermolecular self-association of a chromatin system consisting of saturated 12-mer nucleosome arrays containing various combinations of completely acetylated lysines at positions 5, 8, 12 and 16 of histone H4, induced by the cations Na(+), K(+), Mg(2+), Ca(2+), cobalt-hexammine(3+), spermidine(3+) and spermine(4+). Histones were prepared using a novel semi-synthetic approach with native chemical ligation. Acetylation of H4-K16, but not its glutamine mutation, drastically reduces cation-induced folding of the array. Neither acetylations nor mutations of all the sites K5, K8 and K12 can induce a similar degree of array unfolding. The ubiquitous K(+), (as well as Rb(+) and Cs(+)) showed an unfolding effect on unmodified arrays almost similar to that of H4-K16 acetylation. We propose that K(+) (and Rb(+)/Cs(+)) binding to a site on the H2B histone (R96-L99) disrupts H4K16 epsilon-amino group binding to this specific site, thereby deranging H4 tail-mediated nucleosome-nucleosome stacking and that a similar mechanism operates in the case of H4-K16 acetylation. Inter-array self-association follows electrostatic behavior and is largely insensitive to the position or nature of the H4 tail charge modification.
Journal Article Research Support, Non-U.S. Gov't England
The following values have no corresponding Zotero field: auth-address: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551 Singapore. alt-title: Nucleic acids research number: 5 accession-num: 21047799
Keywords: Protein Conformation; Mutation; Acetylation; Histones/*chemistry/genetics/metabolism; Computer Simulation; Chromatin/chemistry; Cations/chemistry; Lysine/metabolism; Nucleic Acid Conformation; Nucleosomes/*chemistry; Potassium/chemistry; Static Electricity

Protein C-terminal modification through thioacid/azide amidation - Zhang, X.; Li, F.; Lu, X. W.; Liu, C. F. (Bioconjugate Chem., 2009)
The preparation of protein bioconjugates has been largely dependent on the development of selective chemistries that are orthogonal to the diverse functionalities present in a protein. Here, we report a new method for C-terminus-directed modification of recombinant proteins. The method is based on the thioacid/azide amidation reaction. Essentially, hydrothiolytic cleavage of the thioester intermediate in protein splicing yields a recombinant protein with a unique thioacid group at the C-terminus, which is then chemoselectively amidated with an electron-poor organic azide carrying a biofunctional tag. The small ubiquitin protein was used as a model system to demonstrate the utility of this new bioconjugation method. C-terminal PEGylation or biotinylation of ubiquitin was readily achieved through amidation of ubiquitin thioacid with a sulfonazide-functionalized PEG or biotin derivative. Our data validate that thioacid/azide amidation is a mechanistically novel and practically useful method for site-selective protein modification.
The following values have no corresponding Zotero field: auth-address: Division of Chemical Biology and Biotechnology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551. number: 2 edition: 2009/01/15 accession-num: 19140742
Zhang, Xiaohong Li, Fupeng Lu, Xiao-Wei Liu, Chuan-Fa United States Bioconjugate chemistry Bioconjug Chem. 2009 Feb;20(2):197-200. doi: 10.1021/bc800488n.
Keywords: Chromatography, High Pressure Liquid; Amides/*chemistry; Proteins/*chemistry; Sulfur/*chemistry; Ubiquitin/chemistry; Biotinylation; Azides/*chemistry; Polyethylene Glycols/chemistry

Preparation and reactions of N-thioformyl peptides from amino thioacids and isonitriles - Yuan, Yu; Zhu, Jianglong; Li, Xuechen; Wu, Xiangyang; Danishefsky, Samuel J. (Tetrahedron letters, 2009)
The following values have no corresponding Zotero field: number: 20

Dual native chemical ligation at lysine - Yang, R.; Pasunooti, K. K.; Li, F.; Liu, X. W.; Liu, C. F. (J. Am. Chem. Soc., 2009)
A thiol group introduced on the gamma-carbon of lysine mediates robust native chemical ligation at both the alpha- and epsilon-amines in two consecutive steps. Desulfurization then affords the final product, in which the lysine residue at the ligation site has an isopeptide bond on its side chain. The method is useful for the synthesis of proteins containing special post-translational modifications on lysine.
1520-5126 (Electronic) 0002-7863 (Linking) Journal Article Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Division of Chemical Biology and Biotechnology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551. number: 38 accession-num: 19728708
Keywords: Amines/*chemistry; Protein Processing, Post-Translational; Lysine/*chemistry/metabolism; Proteins/*chemical synthesis/metabolism

Low-barrier hydrogen bond in photoactive yellow protein - Yamaguchi, S.; Kamikubo, H.; Kurihara, K.; Kuroki, R.; Niimura, N.; Shimizu, N.; Yamazaki, Y.; Kataoka, M. (Proc. Natl. Acad. Sci. U. S. A., 2009)
Low-barrier hydrogen bonds (LBHBs) have been proposed to play roles in protein functions, including enzymatic catalysis and proton transfer. Transient formation of LBHBs is expected to stabilize specific reaction intermediates. However, based on experimental results and theoretical considerations, arguments against the importance of LBHB in proteins have been raised. The discrepancy is caused by the absence of direct identification of the hydrogen atom position. Here, we show by high-resolution neutron crystallography of photoactive yellow protein (PYP) that a LBHB exists in a protein, even in the ground state. We identified approximately 87% (819/942) of the hydrogen positions in PYP and demonstrated that the hydrogen bond between the chromophore and E46 is a LBHB. This LBHB stabilizes an isolated electric charge buried in the hydrophobic environment of the protein interior. We propose that in the excited state the fast relaxation of the LBHB into a normal hydrogen bond is the trigger for photo-signal propagation to the protein moiety. These results give insights into the novel roles of LBHBs and the mechanism of the formation of LBHBs.
Journal Article Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: Graduate School of Materials Science, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan. alt-title: Proceedings of the National Academy of Sciences of the United States of America number: 2 accession-num: 19122140
Keywords: Protein Conformation; Molecular Structure; *Hydrogen Bonding; Bacterial Proteins/*chemistry; Neutron Diffraction; Photoreceptors, Microbial/*chemistry

N,S Acyl-transfer-mediated synthesis of peptide thioesters using anilide derivatives - Tsuda, Shugo; Shigenaga, Akira; Bando, Kiyomi; Otaka, Akira (Org. Lett., 2009)
null
doi: 10.1021/ol8028093 1523-7060 doi: 10.1021/ol8028093
The following values have no corresponding Zotero field: number: 4 publisher: American Chemical Society

Aminolysis of 3-phenyl propylthiol esters leading to diverse sets of amides - Tomaszewski, Miroslaw J.; Subramanian, Pandiaraju; Santhakumar, Vijayaratnam (Syn. Commun., 2009)
Abstract 3-Phenyl propylthiol esters were investigated as ?activatable? solution phase linkers. These linkers can be activated with silver salts and upon treatment with amines can be converted to the corresponding amides. Under unactivated conditions, the linker is stable to a variety of reagents and reaction conditions including treatment with amines. Abstract 3-Phenyl propylthiol esters were investigated as ?activatable? solution phase linkers. These linkers can be activated with silver salts and upon treatment with amines can be converted to the corresponding amides. Under unactivated conditions, the linker is stable to a variety of reagents and reaction conditions including treatment with amines.
doi: 10.1080/00397910802663352 0039-7911 doi: 10.1080/00397910802663352
The following values have no corresponding Zotero field: number: 14 publisher: Taylor & Francis

Fmoc solid-phase synthesis of C-terminal peptide thioesters by formation of a backbone pyroglutamyl imide moiety - Tofteng, A. Pernille; Sørensen, Kasper K.; Conde-Frieboes, Kilian W.; Hoeg-Jensen, Thomas; Jensen, Knud J. (Angew. Chem. Int. Ed., 2009)
The following values have no corresponding Zotero field: number: 40 publisher: WILEY-VCH Verlag
Keywords: peptides; solid-phase synthesis; thioesters; amide activation; nucleophilic substitution

Chemical synthesis and biotinylation of the thrombospondin domain TSR2 - Tiefenbrunn, T. K.; Dawson, P. E. (Protein Sci., 2009)
The type 1 repeat domain from thrombospondin has potent antiangiogenic activity and a structurally interesting fold, making it an attractive target for protein engineering. Chemical synthesis is an attractive approach for studying protein domains because it enables the use of unnatural amino acids for site-specific labeling and detailed structure-function analysis. Here, we demonstrate the first total chemical synthesis of the thrombospondin type 1 repeat domain by native chemical ligation. In addition to the natural domain, five sites for side chain modification were evaluated and two were found to be compatible with oxidative folding. Several challenges were encountered during peptide synthesis due to the functional complexity of the domain. These challenges were overcome by the use of new solid supports, scavengers, and the testing of multiple ligation sites. We also describe an unusual sequence-specific protecting group migration observed during cleavage resulting in +90 Da and +194 Da adducts. Synthetic access to this domain enables the synthesis of a number of variants that can be used to further our understanding of the biochemical interaction network of thrombospondin and provide insight into the structure and function of this important antitumorogenic protein domain.
R01 GM059380/GM/NIGMS NIH HHS/United States Journal Article Research Support, N.I.H., Extramural United States a publication of the Protein Society
The following values have no corresponding Zotero field: auth-address: Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA. number: 5 accession-num: 19384999
Keywords: Amino Acid Sequence; Humans; Models, Molecular; Molecular Sequence Data; Chromatography, High Pressure Liquid; Protein Folding; Protein Engineering/*methods; *Biotinylation; Peptides/*chemical synthesis/genetics; Protein Interaction Domains and Motifs; Thrombospondin 1/*chemical synthesis/genetics

Phosphate-assisted peptide ligation - Thomas, Gemma L.; Payne, Richard J. (Chem. Commun., 2009)
A novel ligation method for the synthesis of phosphopeptides and peptides is described, which utilises the inherent reactivity of a peptide bearing an N-terminal phosphoserine or phosphothreonine residue to facilitate amide bond formation with a range of C-terminal peptide thioesters.
The following values have no corresponding Zotero field: number: 28 publisher: The Royal Society of Chemistry work-type: 10.1039/B906492C

Stereospecific synthesis of β3-amino acid derivatives from propargylic alcohols: Efficient solution-phase synthesis of oligopeptides without coupling agents - Temperini, Andrea; Terlizzi, Raffaella; Testaferri, Lorenzo; Tiecco, Marcello (Chem. Eur. J., 2009)
A stereospecific synthesis of β3-amino acids has been accomplished starting from readily available and enantioenriched propargylic alcohols. This conversion can be effected in only three steps by selenium-mediated organic transformations of the carbon–carbon triple bond. This method is especially attractive because the reactive Se-phenyl selenocarboxylate intermediates can be trapped with the amine functionality of an amino acid derivative. Through this strategy a chain elongation at the N-terminus has been effected. The N-deprotection and repetition of the homologation with other Se-phenyl selenocarboxylate intermediates produced β- and mixed α/β-oligopeptides without the use of coupling agents.
1521-3765
The following values have no corresponding Zotero field: number: 32 publisher: WILEY-VCH Verlag
Keywords: selenium; amino acids; oligopeptides; propargylic alcohols

Bioorganic synthesis of end-capped anti-HIV peptides by simultaneous cyanocysteine-mediated cleavages of recombinant proteins - Tanaka, M.; Kajiwara, K.; Tokiwa, R.; Watanabe, K.; Ohno, H.; Tsutsumi, H.; Hata, Y.; Izumi, K.; Kodama, E.; Matsuoka, M.; Oishi, S.; Fujii, N. (Bioorg. Med. Chem., 2009)
Bioorganic synthesis of N- and C-terminal end-capped peptides by two simultaneous S-cyanocysteine-mediated cleavages of recombinant proteins is described. This approach is demonstrated in the preparation of anti-HIV fusion inhibitory peptides.
Journal Article Research Support, Non-U.S. Gov't England
The following values have no corresponding Zotero field: auth-address: Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan. alt-title: Bioorganic & medicinal chemistry number: 21 accession-num: 19811922
Keywords: Amino Acid Sequence; Humans; Cysteine/*chemistry; Molecular Sequence Data; Anti-HIV Agents/*chemical synthesis/chemistry/pharmacology; HIV Fusion Inhibitors/*chemical synthesis/chemistry/pharmacology; Peptides/*chemical synthesis/chemistry/pharmacology; Recombinant Fusion Proteins/*metabolism

Protein engineering with the traceless Staudinger ligation - Tam, A.; Raines, R. T. (Methods Enzymol., 2009)
The engineering of proteins can illuminate their biological function and improve their performance in a variety of applications. Within the past decade, methods have been developed that facilitate the ability of chemists to manipulate proteins in a controlled manner. Here, we present the traceless Staudinger ligation as a strategy for the convergent chemical synthesis of proteins. This reaction unites a phosphinothioester and an azide to form an amide bond with no residual atoms. An important feature of this reaction is its ability to ligate peptides at noncysteine residues, thereby overcoming a limitation of alternative strategies. Attributes of the traceless Staudinger ligation are discussed, and an overall comparison of known reagents for effecting the reaction is presented. General methods are elaborated for the synthesis of the most efficacious phosphinothiol for mediating the traceless Staudinger ligation, as well as for the preparation of phosphinothioester and azide fragments and the ligation of peptides immobilized on a solid support. Together, this information facilitates the use of this emerging method to engineer proteins.
1557-7988 (Electronic) 0076-6879 (Linking) Journal Article Research Support, N.I.H., Extramural
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, USA. accession-num: 19632468
Keywords: Animals; Humans; Proteins/*chemical synthesis/chemistry; Peptides/*chemistry; Esters/chemistry; Protein Engineering/*methods; Sulfhydryl Compounds/chemistry; Azides/*chemistry

Catalytic transamidation reactions compatible with tertiary amide metathesis under ambient conditions - Stephenson, N. A.; Zhu, J.; Gellman, S. H.; Stahl, S. S. (J. Am. Chem. Soc., 2009)
The carbon-nitrogen bond of carboxamides is extremely stable under most conditions. The present study reveals that simple zirconium- and hafnium-amido complexes are highly efficient catalysts for equilibrium-controlled transamidation reactions between secondary amines and tertiary amides. In a number of cases, transamidation proceeds rapidly at room temperature. We find that these new catalysts are sufficiently active to promote the metathesis of tertiary amides, which arises from successive transamidation cycles. The catalytic activities we observe are unprecedented and represent a substantial step toward a long-range goal of conducting equilibrium-controlled reactions with carboxamides.
Stephenson, Nickeisha A Zhu, Jiang Gellman, Samuel H Stahl, Shannon S Research Support, U.S. Gov't, Non-P.H.S. United States Journal of the American Chemical Society J Am Chem Soc. 2009 Jul 29;131(29):10003-8. doi: 10.1021/ja8094262.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, USA. number: 29 edition: 2009/07/23 accession-num: 19621957
Keywords: Temperature; Molecular Structure; Catalysis; Amides/*chemical synthesis/*chemistry; Hafnium/*chemistry; Organometallic Compounds/*chemistry; Zirconium/*chemistry

Stability of thioester intermediates in ubiquitin-like modifications - Song, J.; Wang, J.; Jozwiak, A. A.; Hu, W.; Swiderski, P. M.; Chen, Y. (Protein Sci., 2009)
Ubiquitin-like modifications are important mechanisms in cellular regulation, and are carried out through several steps with reaction intermediates being thioester conjugates of ubiquitin-like proteins with E1, E2, and sometimes E3. Despite their importance, a thorough characterization of the intrinsic stability of these thioester intermediates has been lacking. In this study, we investigated the intrinsic stability by using a model compound and the Ubc9 approximately SUMO-1 thioester conjugate. The Ubc9 approximately SUMO-1 thioester intermediate has a half life of approximately 3.6 h (hydrolysis rate k = 5.33 +/- 2.8 x10(-5) s(-1)), and the stability decreased slightly under denaturing conditions (k = 12.5 +/- 1.8 x 10(-5) s(-1)), indicating a moderate effect of the three-dimensional structural context on the stability of these intermediates. Binding to active and inactive E3, (RanBP2) also has only a moderate effect on the hydrolysis rate (13.8 +/- 0.8 x 10(-5) s(-1) for active E3 versus 7.38 +/- 0.7 x 10(-5) s(-1) for inactive E3). The intrinsically high stability of these intermediates suggests that unwanted thioester intermediates may be eliminated enzymatically, such as by thioesterases, to regulate their intracellular abundance and trafficking in the control of ubiquitin-like modifications.
R01GM074748/GM/NIGMS NIH HHS/United States R01GM086171/GM/NIGMS NIH HHS/United States Journal Article Research Support, N.I.H., Extramural United States a publication of the Protein Society
The following values have no corresponding Zotero field: auth-address: Department of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA. number: 12 accession-num: 19785004
Keywords: Humans; Protein Conformation; Hydrolysis; Ubiquitin-Conjugating Enzymes/chemistry/*metabolism; Sulfides/chemistry/*metabolism; SUMO-1 Protein/chemistry/*metabolism

Self-replicating amphiphilic beta-sheet peptides - Rubinov, B.; Wagner, N.; Rapaport, H.; Ashkenasy, G. (Angew. Chem. Int. Ed., 2009)
Rubinov, Boris Wagner, Nathaniel Rapaport, Hanna Ashkenasy, Gonen Germany International ed. in English Angew Chem Int Ed Engl. 2009;48(36):6683-6. doi: 10.1002/anie.200902790.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Ben Gurion University of the Negev, Beer Sheva, 84105, Israel. number: 36 edition: 2009/08/01 accession-num: 19644990 work-type: Research Support, Non-U.S. Gov't
Keywords: Amino Acid Sequence; Kinetics; Peptides/*chemistry; Molecular Structure; Catalysis; Molecular Sequence Data; Circular Dichroism; Protein Structure, Secondary

Semisynthesis of a homogeneous glycoprotein enzyme: ribonuclease C: part 2 - Piontek, C.; Varon Silva, D.; Heinlein, C.; Pohner, C.; Mezzato, S.; Ring, P.; Martin, A.; Schmid, F. X.; Unverzagt, C. (Angew. Chem. Int. Ed., 2009)
Active RNase glycoprotein from three pieces: The glycoprotein enzyme ribonuclease C, which contains a complex saccharide N-glycan, was synthesized by sequential native chemical ligation. An optimized ligation and isolation protocol allowed the efficient assembly and refolding of the 124 amino acid enzyme.
1521-3773 (Electronic) 1433-7851 (Linking) Journal Article Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Bioorganische Chemie, Gebaude NW1, Universitat Bayreuth, 95440 Bayreuth, Germany. number: 11 accession-num: 19180621
Keywords: Ligation; Protein Folding; Carbohydrates/*chemical synthesis/chemistry/isolation & purification; Endoribonucleases/*chemical synthesis/chemistry/isolation & purification; Enzymes/chemical synthesis/chemistry/isolation & purification; Glycopeptides/*chemical synthesis/chemistry/isolation & purification; Glycoproteins/*chemical synthesis/chemistry/isolation & purification; Protein Renaturation

Semisynthesis of a homogeneous glycoprotein enzyme: ribonuclease C: part 1 - Piontek, C.; Ring, P.; Harjes, O.; Heinlein, C.; Mezzato, S.; Lombana, N.; Pohner, C.; Puttner, M.; Varon Silva, D.; Martin, A.; Schmid, F. X.; Unverzagt, C. (Angew. Chem. Int. Ed., 2009)
Seven in one blow: The efficient formation of mixed disulfides on the thiol-rich fusion protein A followed by subsequent intein cleavage gave the fragment B with all seven cysteines protected against oxidation. The native chemical ligation of B with synthetic glycopeptide thioesters provides glycoproteins.
Piontek, Christian Ring, Petra Harjes, Olaf Heinlein, Christian Mezzato, Stefano Lombana, Nelson Pohner, Claudia Puttner, Markus Varon Silva, Daniel Martin, Andreas Schmid, Franz Xaver Unverzagt, Carlo Research Support, Non-U.S. Gov't Germany Angewandte Chemie (International ed. in English) Angew Chem Int Ed Engl. 2009;48(11):1936-40. doi: 10.1002/anie.200804734.
The following values have no corresponding Zotero field: auth-address: Bioorganische Chemie, Gebaude NW1, Universitat Bayreuth, 95440 Bayreuth, Germany. number: 11 edition: 2009/01/29 accession-num: 19173366
Keywords: Ligation; Protein Engineering; Oxidation-Reduction; Protein Folding; Protein Renaturation; Endoribonucleases/biosynthesis/*chemical synthesis/chemistry; Glycopeptides/biosynthesis/*chemical synthesis/chemistry; Glycoproteins/biosynthesis/*chemical synthesis/chemistry; Recombinant Fusion Proteins/biosynthesis/chemical synthesis/chemistry

Silver-catalyzed azaGly ligation. Application to the synthesis of azapeptides and of lipid-peptide conjugates - Ollivier, N.; Besret, S.; Blanpain, A.; Melnyk, O. (Bioconjugate Chem., 2009)
Glycine is a amino acid frequently found in peptides. Substitution of a glycine residue by an azaglycine allows the modulation of peptide conformation, bioactivity, or stability. Azapeptides are usually prepared using solid-phase synthetic procedures. We show here that azaGly peptides can be assembled chemoselectively and without racemization using unprotected peptide fragments by silver-catalyzed reaction of C-terminal peptide hydrazides with N-terminal phenylthiocarbonyl peptides. The reaction was performed in a tBuOH/water mixture and the control of apparent pH permitted the clean formation of the azaGly bond in the presence of lysine residues. We show also that this novel ligation method, called azaGly ligation, can be used for the assembly of lipopeptides. For this, lipid hydrazides were reacted with a phenylthiocarbonyl peptide in the presence of silver ions. This ligation method allows incorporation of acid-sensitive lipid moieties that are incompatible with standard solid-phase peptide synthesis procedures, and more generally should be of interest for the modification of peptides by sensitive acyl moieties.
Ollivier, Nathalie Besret, Soizic Blanpain, Annick Melnyk, Oleg Bioconjug Chem. 2009 Jul;20(7):1397-403. doi: 10.1021/bc9000195.
The following values have no corresponding Zotero field: auth-address: UMR 8161 CNRS/Universite de Lille 1 et 2, Institut Pasteur de Lille, IFR 142 Institut de Biologie de Lille,1 rue du Pr Calmette, 59021 Lille Cedex, France. alt-title: Bioconjugate chemistry number: 7 edition: 2009/06/16 accession-num: 19522459 work-type: Research Support, Non-U.S. Gov't
Keywords: Amino Acid Sequence; Peptides/*chemical synthesis/chemistry; Catalysis; Molecular Sequence Data; Aza Compounds/chemical synthesis/*chemistry; Glycine/chemical synthesis/*chemistry; Lipids/chemical synthesis/*chemistry; Silver/*chemistry

Molecular and cellular specificity of post-translational aminoacyl isomerization in the crustacean hyperglycaemic hormone family - Ollivaux, C.; Gallois, D.; Amiche, M.; Boscameric, M.; Soyez, D. (Febs J., 2009)
D-aminoacyl residues have been detected in various animal peptides from several taxa, especially vertebrates and arthropods. This unusual polymorphism was shown to occur in isoforms of the crustacean hyperglycaemic hormone (CHH) of the American lobster because a D-phenylalanyl residue was found in position 3 of the sequence (CHH and D-Phe3 CHH). In the present study, we report the detailed strategy used to characterize, in the lobster neuroendocrine system, isomers of another member of the CHH family, vitellogenesis inhibiting hormone (VIH). We have demonstrated that the fourth residue is either an L- or a D- tryptophanyl residue (VIH and D-Trp4 VIH). Furthermore, use of antisera specifically recognizing the epimers of CHH and VIH reveals that aminoacyl isomerization occurs in specialized cells of the X organ-sinus gland neurosecretory system and that the D-forms of the two neuropeptides are not only present in the same cells, but, importantly, also are co-packaged within the same secretory vesicles.
Journal Article England
The following values have no corresponding Zotero field: auth-address: Universite Pierre et Marie Curie-Paris 06, UMR 7150 Mer et Sante, Equipe Physiologie Comparee des Erythrocytes, Station Biologique de Roscoff, France. celine.ollivaux@upmc.fr alt-title: The FEBS journal number: 17 accession-num: 19664061
Keywords: Animals; Stereoisomerism; Protein Processing, Post-Translational; Aminoacylation; Arthropod Proteins; Carrier Proteins/metabolism; Invertebrate Hormones/metabolism; Nephropidae/*metabolism; Nerve Tissue Proteins/*metabolism; Neurosecretory Systems/metabolism; Protein Isoforms/metabolism

Efficient substitution reaction from cysteine to the serine residue of glycosylated polypeptide: Repetitive peptide segment ligation strategy and the synthesis of glycosylated tetracontapeptide having acid labile Sialyl-TN antigens - Okamoto, Ryo; Souma, Shingo; Kajihara, Yasuhiro (J. Org. Chem., 2009)
doi: 10.1021/jo8026164 0022-3263 doi: 10.1021/jo8026164
The following values have no corresponding Zotero field: number: 6 publisher: American Chemical Society

Synthesis of peptide thioesters via an N–S acyl shift reaction under mild acidic conditions on an N-4,5-dimethoxy-2-mercaptobenzyl auxiliary group - Nakamura, K.; Kanao, T.; Uesugi, T.; Hara, T.; Sato, T.; Kawakami, T.; Aimoto, S. (J. Pep. Sci., 2009)
1099-1387
The following values have no corresponding Zotero field: number: 11 publisher: John Wiley & Sons, Ltd.
Keywords: peptide thioester; 4,5-dimethoxy-2-mercaptobenzyl (Dmmb) group; Fmoc SPPS; N–S acyl shift; on-resin preparation; thioester-producing resin

Structure-activity analysis of semisynthetic nucleosomes: Mechanistic insights into the stimulation of Dot1L by ubiquitylated histone H2B - McGinty, Robert K.; Köhn, Maja; Chatterjee, Champak; Chiang, Kyle P.; Pratt, Matthew R.; Muir, Tom W. (ACS Chem. Biol., 2014)
doi: 10.1021/cb9002255
The following values have no corresponding Zotero field: number: 11 publisher: American Chemical Society

Semisynthesis of ubiquitylated proteins - McGinty, R. K.; Chatterjee, C.; Muir, T. W. (Methods Enzymol., 2009)
Most, if not all, proteins are at one point or another posttranslationally modified so as to regulate their biological function. One of the most common protein modifications is ubiquitylation, in which the small protein ubiquitin is attached to a target protein in a multistep process involving dedicated ubiquitin ligases. Ubiquitylation is best known for its role in protein turnover. In this case, attachment of a polyubiquitin chain to a target protein leads to its eventual destruction by the 26S proteasome. However, attachment of ubiquitin is not always a kiss of death for the recipient protein; it is increasingly clear that the modification plays additional roles, including regulating protein trafficking and protein signaling. Understanding these functions at the molecular level necessitates that we have access to homogenous ubiquitylated proteins, something that has proved very difficult using standard biochemical approaches. In this chapter, we describe the development of synthetic chemistries and protein semisynthesis methods that permit the site-specific ubiquitylation of proteins. The utility of this methodology is illustrated through the synthesis of ubiquitylated histones.
1557-7988 (Electronic) 0076-6879 (Linking) Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Laboratory of Synthetic Protein Chemistry, Rockefeller University, New York, USA. accession-num: 19632477
Keywords: Animals; Humans; Protein Binding; Proteins/*chemistry/metabolism; *Ubiquitination; *Protein Processing, Post-Translational; Gene Expression; Histones/*chemistry/genetics/metabolism; Peptides/*chemical synthesis; Chromatin/chemistry; Inteins; Mutant Proteins/biosynthesis/genetics/metabolism; Nucleosomes; Photolysis; Recombinant Fusion Proteins/*chemistry/metabolism; Ubiquitin/biosynthesis/genetics

Acetylation of histone H3 at the nucleosome dyad alters DNA-histone binding - Manohar, M.; Mooney, A. M.; North, J. A.; Nakkula, R. J.; Picking, J. W.; Edon, A.; Fishel, R.; Poirier, M. G.; Ottesen, J. J. (J. Biol. Chem., 2009)
Histone post-translational modifications are essential for regulating and facilitating biological processes such as RNA transcription and DNA repair. Fifteen modifications are located in the DNA-histone dyad interface and include the acetylation of H3-K115 (H3-K115Ac) and H3-K122 (H3-K122Ac), but the functional consequences of these modifications are unknown. We have prepared semisynthetic histone H3 acetylated at Lys-115 and/or Lys-122 by expressed protein ligation and incorporated them into single nucleosomes. Competitive reconstitution analysis demonstrated that the acetylation of H3-K115 and H3-K122 reduces the free energy of histone octamer binding. Restriction enzyme kinetic analysis suggests that these histone modifications do not alter DNA accessibility near the sites of modification. However, acetylation of H3-K122 increases the rate of thermal repositioning. Remarkably, Lys --> Gln substitution mutations, which are used to mimic Lys acetylation, do not fully duplicate the effects of the H3-K115Ac or H3-K122Ac modifications. Our results are consistent with the conclusion that acetylation in the dyad interface reduces DNA-histone interaction(s), which may facilitate nucleosome repositioning and/or assembly/disassembly.
0021-9258 (Print) 0021-9258 (Linking) Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Department of Biochemistry, Ohio State University, Columbus, Ohio 43210, USA. number: 35 accession-num: 19520870
Keywords: Animals; Protein Binding; Acetylation; DNA-Binding Proteins/chemistry/metabolism; DNA/*metabolism; Histones/chemical synthesis/*chemistry/*metabolism; Nucleosomes/*chemistry/genetics/metabolism; Xenopus laevis; Xenopus Proteins/chemistry/*metabolism

Synthesis of cyclic peptides through direct aminolysis of peptide thioesters catalyzed by imidazole in aqueous organic solutions - Li, Y.; Yongye, A.; Giulianotti, M.; Martinez-Mayorga, K.; Yu, Y.; Houghten, R. A. (J. Comb. Chem., 2009)
A promising method for the synthesis of cyclic peptides through the direct aminolysis of peptide thioesters is presented. The cyclization step was carried out in a mixture of acetonitrile and 1.5 M aqueous imidazole solution with no observable oligomers. Studies on the N- and C-terminal residues show that the choice of C-terminal residue has a more significant effect on the success rate of cyclization than the choice at the N-terminal residue.
1P41GM079590/GM/NIGMS NIH HHS/United States 1P41GM081261/GM/NIGMS NIH HHS/United States P41 GM079590/GM/NIGMS NIH HHS/United States P41 GM079590-01/GM/NIGMS NIH HHS/United States U54HG03916/HG/NHGRI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. United States
The following values have no corresponding Zotero field: auth-address: Torrey Pines Institute for Molecular Studies, 11350 SW Village Parkway, Port Saint Lucie, Florida 34987, USA. alt-title: Journal of combinatorial chemistry number: 6 accession-num: 19894764
Keywords: Stereoisomerism; Molecular Structure; Catalysis; Sulfhydryl Compounds/*chemical synthesis/chemistry; Cyclization; Peptides, Cyclic/*chemical synthesis/chemistry; Water/chemistry; Acetonitriles/chemistry; Combinatorial Chemistry Techniques/methods; Esters/*chemical synthesis/chemistry; Imidazoles/*chemistry; Solutions

Side-chain assisted ligation in protein synthesis - Kumar, K. S.; Harpaz, Z.; Haj-Yahya, M.; Brik, A. (Bioorg. Med. Chem. Lett., 2009)
Chemical ligation methods for the assembly of functional proteins continue to advance our basic understanding of protein structure and function. In this work, we report on our progress towards the full synthesis of HIV-1 Tat utilizing our newly developed ligation method; side-chain assisted ligation. The HIV-1 Tat was assembled from three fragments wherein the two thioester peptides were synthesized efficiently using the side-chain anchoring strategy following Fmoc-SPPS. The side-chain assisted ligation step was efficient and provided the ligation product in good yield. Following this step, native chemical ligation was used to fully assemble the HIV-1 Tat protein. Although the removal of the auxiliary in small peptides was straightforward, in the case of HIV-1 Tat this step was inefficient thus hampering the completion of the synthesis.
1464-3405 (Electronic) 0960-894X (Linking) Journal Article Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel. number: 14 accession-num: 19376701
Keywords: Amino Acid Sequence; Molecular Sequence Data; Chromatography, High Pressure Liquid; Dipeptides/*chemistry; Spectrometry, Mass, Electrospray Ionization; synthesis/chemistry; tat Gene Products, Human Immunodeficiency Virus/*chemical

Total chemical synthesis of proteins - Kent, S. B. H. (Chem. Soc. Rev., 2009)
This tutorial review outlines the modern ligation methods that enable the efficient total chemical synthesis of enzymes and other protein molecules. Key to this success is the chemoselective reaction of unprotected synthetic peptides ('chemical ligation'). Notably, native chemical ligation enables the reaction of two unprotected peptides in aqueous solution at neutral pH to form a single product in near quantitative yield. Full-length synthetic polypeptides are folded to form the defined tertiary structure of the target protein molecule, which is characterized by mass spectrometry, NMR, and X-ray crystallography, in addition to biochemical and/or biological activity.
0306-0012 (Print) 0306-0012 (Linking) Journal Article Review
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Institute for Biophysical Dynamics, Center for Integrative Science, University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA. skent@uchicago.edu number: 2 accession-num: 19169452
Keywords: Humans; Protein Conformation; Cysteine/chemistry; Mass Spectrometry; Crystallography, X-Ray; Magnetic Resonance Spectroscopy; Proteins/*chemical synthesis/chemistry/classification/isolation &; purification

The use of a cysteinyl prolyl ester (CPE) autoactivating unit in peptide ligation reactions - Kawakami, T.; Aimoto, S. (Tetrahedron, 2009)
Keywords: #nosource

Peptide ligation via the in-situ transformation of an amide into a thioester at a cysteine residue - Kawakami, T.; Aimoto, S. (Adv. Exp. Med. Biol., 2009)
0065-2598 (Print) 0065-2598 (Linking) Journal Article Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan. accession-num: 19400119
Keywords: Peptides/*chemistry; Cysteine/*chemistry; Amides/*chemistry; Esters/*chemistry

3-Mercaptopropionic acid-mediated synthesis of peptide and protein thioesters - Kang, J.; Richardson, J. P.; Macmillan, D. (Chem. Commun., 2009)
Peptides and proteins fragment sequence-specifically in the presence of 3-mercaptopropionic acid to afford thioesters which can be used in native chemical ligation reactions.
1359-7345 (Print) 1359-7345 (Linking) Journal Article Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, University College London, 20 Gordon Street, London, UK. number: 4 accession-num: 19137167
Keywords: Proteins/*chemical synthesis/chemistry; Peptides/*chemical synthesis/chemistry; 3-Mercaptopropionic Acid/*chemistry

Toward homogeneous erythropoietin: chemical synthesis of the Ala1-Gly28 glycopeptide domain by "alanine" ligation - Kan, C.; Trzupek, J. D.; Wu, B.; Wan, Q.; Chen, G.; Tan, Z.; Yuan, Y.; Danishefsky, S. J. (J. Am. Chem. Soc., 2009)
The Ala(1)-Gly(28) glycopeptide fragment (28) of EPO was prepared by chemical synthesis as a single glycoform. Key steps in the synthesis include attachment of a complex dodecasaccharide (7) to a seven amino acid peptide via Lansbury aspartylation, native chemical ligation to join peptide 19 with the glycopeptide domain 18, and a selective desulfurization at the ligation site to reveal the natural Ala(19). This glycopeptide fragment (28) contains both the requisite N-linked dodecasaccharide and a C-terminal (alpha)thioester handle, the latter feature permitting direct coupling with a glycopeptide fragment bearing N-terminal Cys(29) without further functionalization.
1520-5126 (Electronic) 0002-7863 (Linking) Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.
The following values have no corresponding Zotero field: auth-address: Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10065, USA. number: 15 accession-num: 19334679

Protein autoproteolysis: Conformational strain linked to the rate of peptide cleavage by the pH dependence of the N-O acyl shift reaction - Johansson, Denny G. A.; Wallin, Göran; Sandberg, Anders; Macao, Bertil; Aqvist, Johan; Härd, Torleif (J. Am. Chem. Soc., 2015)
doi: 10.1021/ja9010817
doi: 10.1021/ja9010817
The following values have no corresponding Zotero field: number: 27 publisher: American Chemical Society
The following values have no corresponding Zotero field: number: 27 publisher: American Chemical Society

Hydrogels cross-linked by native chemical ligation - Hu, Bi-Huang; Su, Jing; Messersmith, Phillip B. (Biomacromolecules, 2009)
We describe the use of native chemical ligation (NCL) reaction to covalently cross-link soluble polymers into hydrogels. Macromonomers consisting of a four-armed poly(ethylene glycol) (PEG) core end-functionalized with either thioester or N-terminal cysteine peptide were designed and synthesized. Upon mixing aqueous solutions of the thioester and N-terminal cysteine macromonomers, rigid hydrogels formed within minutes. The gelation time was affected by choice of buffer, pH, polymer concentration, reaction temperature, and chemical composition of the N-terminal cysteine conjugate. The kinetics of gel formation and the viscoelastic behavior of selected hydrogels were further studied by oscillatory rheology, which demonstrated a minimum gel formation time of approximately two minutes and the formation of an elastic cross-linked hydrogel via the NCL reaction. A useful feature of this hydrogel strategy is the regeneration of thiol functional groups as a result of the NCL reaction, thereby allowing functionalization of the polymer hydrogel with biomolecules. This was demonstrated by conjugation of a maleimide-GRGDSPG-NH(2) peptide to an NCL hydrogel, permitting the attachment of human mesenchymal stem cells (hMSCs) on the hydrogel. Due to the mild reaction conditions, chemoselectivity, and potential for biological functionalization, our approach may prove useful as a general method for hydrogel formation, including hydrogels intended for biomedical applications.
19601644[pmid] Biomacromolecules
The following values have no corresponding Zotero field: number: 8 accession-num: PMC2790863

Internal cysteine accelerates thioester-based peptide ligation - Haase, Christian; Seitz, Oliver (Eur. J. Org. Chem., 2009)
Thioester-mediated peptide coupling reactions are powerful tools in protein synthesis. The fragment coupling occurs extremely fast at ligation sites that contain an N-terminal cysteine residue. This native chemical ligation involves a capture step that affixes the acyl component in the immediate vicinity of the N-terminal amino group. The subsequent intramolecular S,N-acyl transfer step proceeds via an entropically favored five-membered ring intermediate. In this study we investigated whether sequence internal cysteine residues that lead to the formation of macrocyclic intermediates are also able to accelerate the rate of thioester-based fragment couplings. It was the aim to identify distance requirements that enable internal cysteine-mediated ligation reactions to proceed at synthetically useful rates. It was found that appropriately positioned cysteine residues can induce up to 25-fold rate enhancements compared to a cysteine-lacking control peptide. Highest ligation rates and yields were obtained when the internal thiol amino acid was incorporated at the fifth or sixth position from the N-terminus of the C-terminal coupling segment. The findings reveal a correlation between the size of the macrocyclic ring intermediate and the ease of the peptide ligation. Internal cysteine ligation may provide the opportunity to shift amino acid cysteine bonds that are difficult to access through native chemical ligation (such as Pro–Cys bonds) by 4–5 amino acids to the N-terminus.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
1099-0690
The following values have no corresponding Zotero field: number: 13 publisher: WILEY-VCH Verlag
Keywords: Coupling; Macrocycles; Peptides; Synthetic methods; Thioester

Gaussian 09. Revision A.02 - Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; et al. (Gaussian, Inc., 2009)
Keywords: #nosource

Expressed protein ligation (EPL) in the study of signal transduction, ion conduction, and chromatin biology - Flavell, R. R.; Muir, T. W. (Acc. Chem. Res., 2009)
Expressed protein ligation (EPL) is a semisynthetic technique in which a recombinant protein thioester, generated by thiolysis of an intein fusion protein, is reacted with a synthetic or recombinant peptide with an N-terminal cysteine to produce a native peptide bond. This method has been used extensively for the incorporation of biophysical probes, unnatural amino acids, and post-translational modifications in proteins. In the 10 years since this technique was developed, the applications of EPL to studying protein structure and function have grown ever more sophisticated. In this Account, we review the use of EPL in selected systems in which substantial mechanistic insights have recently been gained through the use of the semisynthetic protein derivatives. EPL has been used in many studies to unravel the complexity of signaling networks and subcellular trafficking. Herein, we highlight this application to two different systems. First, we describe how phosphorylated or otherwise modified proteins in the TGF-beta signaling network were prepared and how they were applied to understanding the complexities of this pathway, from receptor activation to nuclear import. Second, Rab-GTPases are multiply modified with lipid derivatives, and EPL-based techniques were used to incorporate these modifications, allowing for the elucidation of the biophysical basis of membrane association and dissociation. We also review the use of EPL to understand the biology of two other systems, the potassium channel KcsA and histones. EPL was used to incorporate d-alanine and an amide-to-ester backbone modification in the selectivity filter of the KcsA potassium channel, providing insight into the mechanism of selectivity in ion conduction. In the case of histones, which are among the most heavily post-translationally modified proteins, the modifications play a key role in the regulation of gene transcription and chromatin structure. We describe how native chemical ligation and EPL were used to generate acetylated, phosphorylated, methylated, and ubiquitylated histones and how these modified histones were used to interrogate chromatin biology. Collectively, these studies demonstrate the utility of EPL in protein science. These techniques and concepts are applicable to many other systems, and ongoing advances promise to extend this semisynthetic technique to increasingly complex biological problems.
1520-4898 (Electronic) 0001-4842 (Linking) Journal Article Research Support, N.I.H., Extramural Review
The following values have no corresponding Zotero field: auth-address: Laboratory of Synthetic Protein Chemistry, The Rockefeller University, New York, New York 10065, USA. number: 1 accession-num: 18939858
Keywords: Models, Molecular; Protein Conformation; Molecular Structure; *Protein Splicing; Chromatin/genetics/*metabolism; Histones/chemistry/genetics/metabolism; Ions/*metabolism; Potassium Channels/chemistry/genetics/metabolism; rab GTP-Binding Proteins/chemistry/genetics/metabolism; Recombinant Proteins/*chemistry/genetics/metabolism; Signal Transduction/*physiology; Smad2 Protein/chemistry/genetics/metabolism; Transforming Growth Factor beta/chemistry/genetics/metabolism

Matrix photochemistry, photoelectron spectroscopy, solid-phase structure, and ring strain energy of beta-propiothiolactone - Dugarte, N. Y.; Erben, M. F.; Romano, R. M.; Boese, R.; Ge, M. F.; Li, Y.; Della Védova, Carlos O. (J. Phys. Chem. A, 2009)
The four-membered heterocyclic beta-propiothiolactone compound was isolated in a low-temperature inert Ar matrix, and the UV-visible (200 < or = lambda < or = 800 nm) induced photochemistry was studied. On the basis of the IR spectra, the formation of methylketene (CH(3)CHCO) was identified as the main channel of photodecomposition. The formation of ethene and thiirane, with the concomitant elimination of OCS and CO, respectively, was also observed as minor decomposition channels. The valence electronic structure was investigated by HeI photoelectron spectroscopy assisted by quantum chemical calculations at the OVGF/6-311++G(d,p) level of theory. The first three bands at 9.73, 9.87, and 12.06 eV are ascribed to the n''(S), n'(O), and pi''(CO) orbitals, respectively, denoting the importance of the -SC(O)- group in the outermost electronic properties. Additionally, the structure of a single crystal, grown in situ, was determined by X-ray diffraction analysis at low temperature. The crystalline solid [monoclinic system, P21/c, a = 8.1062(1) A, b = 10.3069(2) A, c = 10.2734(1) A, beta = 107.628(1) degrees, and Z = 8] consists of planar molecules arranged in layers. The skeletal parameters, especially the valence angles [angleC2-C1-S = 94.55(7) degrees, angleOC-C = 134.20(11) degrees, angleC-S-C = 77.27(5) degrees], differ from those typically found in acyclic thioester compounds, suggesting the presence of strong strain effects. The conventional ring strain energy was determined to be 16.4 kcal/mol at the G2MP2 level of calculation within the hyperhomodesmotic model.
Journal Article Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: CEQUINOR (UNLP-CONICET, CCT-La Plata), Departamento de Quimica, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CC 962 (1900), La Plata, Republica Argentina. alt-title: The journal of physical chemistry number: 15 accession-num: 19301891
Keywords: Temperature; Ultraviolet Rays; *Electrons; Crystallography, X-Ray; Quantum Theory; Spectrophotometry, Infrared; *Photochemical Processes/radiation effects; Gases/chemistry; Propiolactone/*analogs & derivatives/chemistry; Vibration

Reaction of Thioacids with Isocyanates and Isothiocyanates: A Convenient Amide Ligation Process - Crich, David; Sasaki, Kaname (Org. Lett., 2013)
doi: 10.1021/ol901370y
The following values have no corresponding Zotero field: number: 15 publisher: American Chemical Society

SN2-type nucleophilic opening of b-thiolactones (thietan-2-ones) as a source of thioacids for coupling reactions - Crich, David; Sana, Kasinath (J. Org. Chem., 2009)
doi: 10.1021/jo9001728 0022-3263 doi: 10.1021/jo9001728
The following values have no corresponding Zotero field: number: 9 publisher: American Chemical Society

Efficient use of the Dmab protecting group: applications for the solid-phase synthesis of N-linked glycopeptides - Conroy, Trent; Jolliffe, Katrina A.; Payne, Richard J. (Org. Biomol. Chem., 2009)
An efficient protocol for the chemoselective removal of Dmab esters on the solid phase is reported; this method has been successfully utilised for the convergent solid phase synthesis of N-linked glycopeptides.
1477-0520 10.1039/B821051A
The following values have no corresponding Zotero field: number: 11 publisher: The Royal Society of Chemistry

Semisynthesis of membrane-attached prion proteins - Chu, N. K.; Becker, C. F. (Methods Enzymol., 2009)
Conversion of cellular prion protein (PrP(C)) into the pathological conformer (PrP(Sc)) is the hallmark of prion diseases and has been studied extensively by using recombinantly expressed PrP (rPrP). Because of the inherent difficulties of expressing and purifying posttranslationally modified rPrP variants only a limited amount of data is available for membrane-associated PrP and its behavior in vitro and in vivo. Protein semisynthesis provides two alternative routes to access multimilligram amounts of membrane-attached rPrP, which are described in detail here. In both cases, rPrP fused to a C-terminal extension comprising either the Mycobacterium xenopi GyrA mini-intein or the Synechocystis sp. DnaE N-terminal split intein is expressed in E. coli. Protein purification was followed by reaction with chemically synthesized palmitoylated membrane anchor peptides to yield rPrP(Palm) or with a chemically synthesized glycosylphosphatidylinositol (GPI) anchor to give rPrP(GPI). Solubility problems encountered with synthetic membrane anchors were overcome by either incorporating a polyethylene glycol-based C-terminal tag (removable by specific proteolysis) or by direct incorporation into liposomes. The new rPrP(Palm) variants studied by a variety of in vitro methods exhibited a high affinity to liposomes and an increased lag phase during aggregation when compared to rPrP. Similar results were obtained for rPrP(GPI), in which only one alkyl chain is sufficient for quantitative membrane attachment. In vivo studies demonstrated that double lipidated rPrP(Palm) is efficiently taken up into the membranes of mouse neuronal and human epithelial kidney cells.
Journal Article United States
The following values have no corresponding Zotero field: auth-address: Technische Universitat Munchen, Department of Chemistry, Protein Chemistry Group, Garching, Germany. alt-title: Methods in enzymology accession-num: 19632475
Keywords: Amino Acid Sequence; Animals; Humans; Protein Binding; Molecular Sequence Data; Protein Splicing; Gene Expression; Protein Processing, Post-Translational; Inteins; Cell Membrane/*metabolism; Glycosylphosphatidylinositols/chemistry; Liposomes/metabolism; Lipoylation; Membrane Proteins/*chemistry; Palmitic Acid/chemistry; Peptides/*chemical synthesis/metabolism; PrPC Proteins/*chemistry/isolation & purification/*metabolism; Recombinant Fusion Proteins/biosynthesis/chemistry/isolation & purification

A semisynthetic strategy to generate phosphorylated and acetylated histone H2B - Chiang, K. P.; Jensen, M. S.; McGinty, R. K.; Muir, T. W. (ChemBioChem, 2009)
1439-7633 (Electronic) 1439-4227 (Linking) Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Laboratory of Synthetic Protein Chemistry, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. number: 13 accession-num: 19623598
Keywords: Acetylation; Phosphorylation; Protein Processing, Post-Translational; Recombinant Proteins/chemistry/metabolism; Antibodies/immunology/metabolism; Histones/*chemistry/metabolism

Chemical modification of proteins at cysteine: opportunities in chemistry and biology - Chalker, J. M.; Bernardes, G. J.; Lin, Y. A.; Davis, B. G. (Chem. Asian J., 2009)
Chemical modification of proteins is a rapidly expanding area in chemical biology. Selective installation of biochemical probes has led to a better understanding of natural protein modification and macromolecular function. In other cases such chemical alterations have changed the protein function entirely. Additionally, tethering therapeutic cargo to proteins has proven invaluable in campaigns against disease. For controlled, selective access to such modified proteins, a unique chemical handle is required. Cysteine, with its unique reactivity, has long been used for such modifications. Cysteine has enjoyed widespread use in selective protein modification, yet new applications and even new reactions continue to emerge. This Focus Review highlights the enduring utility of cysteine in protein modification with special focus on recent innovations in chemistry and biology associated with such modifications.
Journal Article Research Support, Non-U.S. Gov't Review Germany
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford OX1 3TA, UK. alt-title: Chemistry, an Asian journal number: 5 accession-num: 19235822
Keywords: Proteins/*chemistry/metabolism; Cysteine/*chemistry/metabolism; Oxidation-Reduction; Protein Processing, Post-Translational; Alkylation; Disulfides/chemistry

Synthesis of an iberiotoxin derivative by chemical ligation: a method for improved yields of cysteine-rich scorpion toxin peptides - Bingham, J. P.; Chun, J. B.; Ruzicka, M. R.; Li, Q. X.; Tan, Z. Y.; Kaulin, Y. A.; Englebretsen, D. R.; Moczydlowski, E. G. (Peptides, 2009)
Automated and manual solid phase peptide synthesis techniques were combined with chemical ligation to produce a 37-residue peptide toxin derivative of iberiotoxin which contained: (i) substitution of Val(16) to Ala, to facilitate kinetic feasibility of native chemical ligation, and; (ii) substitution of Asp(19) to orthogonally protected Cys-4-MeOBzl for chemical conjugate derivatization following peptide folding and oxidation. This peptide ligation approach increased synthetic yields approximately 12-fold compared to standard linear peptide synthesis. In a functional inhibition assay, the ligated scorpion toxin derivative, iberiotoxin V16A/D19-Cys-4-MeOBzl, exhibited 'native-like' affinity (K(d)=1.9 nM) and specificity towards the BK Ca(2+)-activated K(+) Channel (K(Ca)1.1). This was characterized by the rapid association and slow dissociation rates (k(on)=4.59 x 10(5)M(-1)s(-1); k(off)=8.65 x 10(-4) s(-1)) as determined by inhibition of macroscopic whole-cell currents of cloned human K(Ca)1.1 channel. These results illustrate the successful application of peptide chemical ligation to improve yield of cysteine-rich peptide toxins over traditional solid phase peptide synthesis. Native chemical ligation is a promising method for improving production of biologically active disulfide containing peptide toxins, which have diverse applications in studies of ion-channel function.
P01 NS042202/NS/NINDS NIH HHS/United States P01 NS042202-010001/NS/NINDS NIH HHS/United States P01 NS042202-010002/NS/NINDS NIH HHS/United States Journal Article Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: Department of Molecular Biosciences and Bioengineering, College of Tropical Agriculture and Human Resources, University of Hawaii, Honolulu, HI 96822, USA. jbingham@hawaii.edu alt-title: Peptides number: 6 accession-num: 19463736
Keywords: Humans; Kinetics; Cell Line; Protein Folding; Cysteine/analysis/*chemistry; Large-Conductance Calcium-Activated Potassium Channels/drug effects; Patch-Clamp Techniques; Peptide Fragments/*chemical synthesis/chemistry/pharmacology; Peptides/*chemical synthesis/*chemistry/pharmacology; Scorpion Venoms/*chemical synthesis/*chemistry/pharmacology

Principles of ubiquitin and SUMO modifications in DNA repair - Bergink, S.; Jentsch, S. (Nature, 2009)
With the discovery in the late 1980s that the DNA-repair gene RAD6 encodes a ubiquitin-conjugating enzyme, it became clear that protein modification by ubiquitin conjugation has a much broader significance than had previously been assumed. Now, two decades later, ubiquitin and its cousin SUMO are implicated in a range of human diseases, including breast cancer and Fanconi anaemia, giving fresh momentum to studies focused on the relationships between ubiquitin, SUMO and DNA-repair pathways.
Bergink, Steven Jentsch, Stefan Research Support, Non-U.S. Gov't Review England Nature Nature. 2009 Mar 26;458(7237):461-7. doi: 10.1038/nature07963.
The following values have no corresponding Zotero field: auth-address: Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany. number: 7237 edition: 2009/03/28 accession-num: 19325626
Keywords: Animals; Humans; Phosphorylation; Ubiquitin/*metabolism; Ubiquitination; *DNA Repair; Proliferating Cell Nuclear Antigen/metabolism; SUMO-1 Protein/*metabolism

MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria - Banci, Lucia; Bertini, Ivano; Cefaro, Chiara; Ciofi-Baffoni, Simone; Gallo, Angelo; Martinelli, Manuele; Sideris, Dionisia P.; Katrakili, Nitsa; Tokatlidis, Kostas (Nat. Struct. Mol. Biol., 2009)
The following values have no corresponding Zotero field: publisher: Nature Publishing Group work-type: Article

Cytokine Antagonists for the Treatment of Asthma: Progress to Date - Antoniu, Sabina Antonela (BioDrugs, 2009)
Asthma is a disease of the airways in which several cytokines such as interleukin (IL)-4, IL-5, IL-13 and tumor necrosis factor-[alpha] (TNF[alpha]) play a major role in the development and progression of inflammation, airway hyperresponsiveness, mucus production, and airway remodeling. The conventional anti-inflammatory therapies, represented by inhaled corticosteroids and antileukotrienes, are not always able to provide optimal disease control and it is therefore hoped that cytokine antagonists could achieve this goal in such situations. Anticytokine therapies have been tested in preclinical studies and some have entered clinical trials. Anti-IL-4 therapies have been tested in animal models of allergy-related asthma, but because of unclear efficacy their development was discontinued. However, IL-4/IL-13 dual antagonists and IL-13-specific blocking agents are more promising, as they exhibit more sustained anti-inflammatory effects. IL-5 antagonists have been found to be of limited efficacy in clinical studies but might be useful in conditions characterized by severe hypereosinophilia, and in which asthma is one of the disease manifestations. Unlike other chronic inflammatory conditions, such as rheumatoid arthritis, the use of anti-TNF[alpha] therapies in asthma might be limited by the unfavorable risk/benefit ratio associated with long-term use. The identification of so-called asthma TNF[alpha] phenotypes and perhaps the use of a less aggressive treatment regimen might address this important aspect. Other cytokine antagonists (for example for IL-9 or IL-25) are currently being evaluated in the asthma setting, and could open new therapeutic perspectives based on their efficacy and safety. Copyright 2009 Adis Data Information BV
The following values have no corresponding Zotero field: number: 4
Keywords: 00063030-200923040-00004; Asthma; Cytokine-inhibitors, general; Cytokine-targets; Cytokines, general; Interleukin-inhibitors, general; Tumour-necrosis-factor-inhibitos, general

Highly efficient and chemoselective peptide ubiquitylation - Ajish Kumar, K. S.; Haj-Yahya, Mahmood; Olschewski, Diana; Lashuel, Hilal A.; Brik, Ashraf (Angew. Chem. Int. Ed., 2009)
1521-3773
The following values have no corresponding Zotero field: number: 43 publisher: WILEY-VCH Verlag
Keywords: ubiquitin; peptides; desulfurization; bioorganic chemistry; protein modification

Solid-phase synthesis of peptide thioacids through hydrothiolysis of resin-bound peptide thioesters - Zhang, Xiaohong; Lu, Xiao-Wei; Liu, Chuan-Fa (Tetrahedron Lett., 2008)
The following values have no corresponding Zotero field: number: 42

Silica gel accelerated aza-Michael addition of amines to a,b-unsaturated amides - You, Lisha; Feng, Song; An, Rui; Wang, Xinhong; Bai, Donglu (Tetrahedron Lett., 2008)
A novel method to synthesize Î²-amino amide has been developed via conjugated addition of amine to bulky Î±,Î²-unsaturated amides promoted by silica gel. The silica gel worked efficiently to accelerate the reaction and afforded the related adduct in good to excellent yield.
0040-4039
The following values have no corresponding Zotero field: number: 35
Keywords: Amines; Aza-Michael addition; Î±,Î²-Unsaturated amides; Silica gel

pKa-dependent formation of amides in water from an acyl phosphate monoester and amines - Wodzinska, Jolanta; Kluger, Ronald (J. Org. Chem., 2008)
doi: 10.1021/jo800667b 0022-3263 doi: 10.1021/jo800667b
The following values have no corresponding Zotero field: number: 12 publisher: American Chemical Society

Monitoring of native chemical ligation on solid substrate by surface plasmon resonance - Wieczerzak, Ewa; Hamel, Raymond; Chabot, Vincent; Aimez, Vincent; Grandbois, Michel; Charette, Paul G.; Escher, Emanuel (Pept. Sci., 2008)
During the last years native chemical ligation (NCL) gained in popularity as a method allowing the chemical synthesis of large peptides and entire proteins. NCL is particularly well-suited for chemoselective and nondenaturing attachment of biomolecules on solid substrates. In the present work, we show the feasibility of monitoring of peptide synthesis, NCL and its catalysis on silicon oxide modified gold surfaces by surface plasmon resonance (SPR). NCL of a model peptide—bradykinin thioester—was carried out and monitored with a custom-built SPR apparatus. Solid-phase produced bradykinin thioester was ligated to the surface in the presence of variable concentrations of 4-mercaptophenylacetic acid as transthioesterification catalyst. At catalyst concentration of 48 mM and above, the NCL reaction was maximal and identical to the reaction of the purified peptide-mercaptophenylacetic acid thioester. SPR curves indicate typical first-order kinetics with t1/2 of 81 s for this aryl thioester, but of 104 min for the primary alkyl thioester. © 2008 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90: 415–420, 2008. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
1097-0282
The following values have no corresponding Zotero field: number: 3 publisher: Wiley Subscription Services, Inc., A Wiley Company
Keywords: peptide synthesis; biosensor; native chemical ligation (NCL); surface plasmon resonance (SPR)

A simple method for preparing peptide C-terminal thioacids and their application in sequential chemoenzymatic ligation - Tan, X. H.; Zhang, X.; Yang, R.; Liu, C. F. (ChemBioChem, 2008)
Tan, Xiao-Hong Zhang, Xiaohong Yang, Renliang Liu, Chuan-Fa Research Support, Non-U.S. Gov't Germany Chembiochem : a European journal of chemical biology Chembiochem. 2008 May 5;9(7):1052-6. doi: 10.1002/cbic.200700740.
The following values have no corresponding Zotero field: auth-address: Division of Chemical Biology and Biotechnology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore. number: 7 edition: 2008/04/10 accession-num: 18398882
Keywords: Peptides/*chemistry; Esters/chemistry; Chromatography, High Pressure Liquid; Hydrolysis; Sulfhydryl Compounds/*chemical synthesis/*chemistry; Models, Chemical; Acids/chemical synthesis/*chemistry

Comparative properties of insulin-like growth factor 1 (IGF-1) and [Gly7D-Ala]IGF-1 prepared by total chemical synthesis - Sohma, Y.; Pentelute, B. L.; Whittaker, J.; Hua, Q. X.; Whittaker, L. J.; Weiss, M. A.; Kent, S. B. H. (Angew Chem Int Ed Engl, 2008)
DK065890/DK/NIDDK NIH HHS/United States DK40949/DK/NIDDK NIH HHS/United States Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Germany
The following values have no corresponding Zotero field: auth-address: Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, The University of Chicago, Chicago IL 60637, USA. alt-title: Angewandte Chemie (International ed number: 6 accession-num: 18161716
Keywords: Models, Molecular; Protein Binding; Protein Folding; Protein Structure, Tertiary; Nuclear Magnetic Resonance, Biomolecular; Alanine/chemistry; Glycine/chemistry; Insulin-Like Growth Factor I/*analogs & derivatives/*chemical; Receptor, IGF Type 1/metabolism; synthesis/chemistry/metabolism

Ca2+-mediated thiolysis of peptide–resin linkage as an option for preparing protected peptide thioesters - Proti, Patrícia B.; Miranda, M. Terêsa M. (Tetrahedron Lett., 2008)
A mild new procedure for preparing protected peptide thioesters, based on Ca2+-assisted thiolysis of peptide–Kaiser oxime resin (KOR) linkage, is described. Ac-Ile-Ser(Bzl)-Asp(OcHx)-SR (Ac: acetyl; Bzl: benzyl; cHx: cyclohexyl), model peptide, was readily released from the resin by incubating the peptide–KOR at 60°C in mixtures of DMF with n-butanethiol [R=(CH2)3CH3] or ethyl 3-mercaptopropionate [R=(CH2)2COOCH2CH3] containing Ca(CH3COO)2. After serine and aspartic acid side-chain deprotection under acid conditions, Ac-Ile-Ser-Asp-S(CH2)2COOCH2CH3 was successfully obtained with good quality and high yield. This type of C-terminal modified peptide may act as an excellent acyl donor in peptide segment condensation by the thioester method, native chemical ligation and enzymatic methods.
The following values have no corresponding Zotero field: number: 24
Keywords: -Butanethiol; Ethyl 3-mercaptopropionate; Kaiser oxime resin; Metal ion; Solid-phase peptide synthesis

Organocatalytic asymmetric addition of alcohols and thiols to activated electrophiles: Efficient dynamic kinetic resolution and desymmetrization protocols - Peschiulli, Aldo; Quigley, Cormac; Tallon, Sean; Gun'ko, Yuri K.; Connon, Stephen J. (J. Org. Chem., 2008)
(Chemical Equation Presented) Bifunctional urea-based cinchona alkaloid derivatives have been shown to promote highly efficient DKR reactions of azalactones using an alcohol nucleophile. The optimum catalyst is remarkably insensitive to the steric bulk of the amino acid residue, allowing alanine-, methionine-, and phenylalanine-derived azalactones to undergo DKR with unprecedented levels of enantioselectivity using a synthetic catalyst. The first DKR of these substrates by thiols and the highly enantioselective desymmetrization of a meso-glutaric anhydride by thiolysis are also reported.
The following values have no corresponding Zotero field: number: 16
Keywords: #nosource

Cysteine-free peptide and glycopeptide ligation by direct aminolysis - Payne, R. J.; Ficht, S.; Greenberg, W. A.; Wong, C. H. (Angew. Chem. Int. Ed., 2008)
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Germany
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. alt-title: Angewandte Chemie (International ed number: 23 accession-num: 18442150
Keywords: Amino Acid Sequence; Peptides/*chemical synthesis/chemistry; Cysteine/*chemistry; Molecular Sequence Data; Amines/*chemistry; Methods; Glycopeptides/*chemical synthesis/chemistry

Selenopeptide chemistry - Muttenthaler, M.; Alewood, P. F. (J. Pept. Sci., 2008)
This review focuses on the chemical aspects of the 21st proteinogenic amino acid, selenocysteine in peptides and proteins. It describes the physicochemical properties of selenium/sulfur and selenocysteine/cysteine based on comprehensive structural (X-ray, NMR, CD) and biological data, and illustrates why selenocysteine is considered the most conservative substitution of cysteine. The main focus lies on the synthetic methods on selenocysteine incorporation into peptides and proteins, including an overview of the selenocysteine building block syntheses for Boc- and Fmoc-SPPS. Selenocysteine-mediated reactions such as native chemical ligation and dehydroalanine formation are addressed towards peptide conjugation. Selenopeptides have very interesting and distinct properties which lead to a diverse range of applications such as structural, functional and mechanistic probes, robust scaffolds, enzymatic reaction design, peptide conjugations and folding tools.
1075-2617 (Print) 1075-2617 (Linking) Journal Article
The following values have no corresponding Zotero field: auth-address: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Australia. number: 12 accession-num: 18951416
Keywords: Molecular Structure; Selenocysteine/chemistry; Selenium/chemistry; Selenoproteins/*chemical synthesis/*chemistry

Chemically ubiquitylated histone H2B stimulates hDot1L-mediated intranucleosomal methylation - McGinty, R. K.; Kim, J.; Chatterjee, C.; Roeder, R. G.; Muir, T. W. (Nature, 2008)
Numerous post-translational modifications of histones have been described in organisms ranging from yeast to humans. Growing evidence for dynamic regulation of these modifications, position- and modification-specific protein interactions, and biochemical crosstalk between modifications has strengthened the 'histone code' hypothesis, in which histone modifications are integral to choreographing the expression of the genome. One such modification, ubiquitylation of histone H2B (uH2B) on lysine 120 (K120) in humans, and lysine 123 in yeast, has been correlated with enhanced methylation of lysine 79 (K79) of histone H3 (refs 5-8), by K79-specific methyltransferase Dot1 (KMT4). However, the specific function of uH2B in this crosstalk pathway is not understood. Here we demonstrate, using chemically ubiquitylated H2B, a direct stimulation of hDot1L-mediated intranucleosomal methylation of H3 K79. Two traceless orthogonal expressed protein ligation (EPL) reactions were used to ubiquitylate H2B site-specifically. This strategy, using a photolytic ligation auxiliary and a desulphurization reaction, should be generally applicable to the chemical ubiquitylation of other proteins. Reconstitution of our uH2B into chemically defined nucleosomes, followed by biochemical analysis, revealed that uH2B directly activates methylation of H3 K79 by hDot1L. This effect is mediated through the catalytic domain of hDot1L, most likely through allosteric mechanisms. Furthermore, asymmetric incorporation of uH2B into dinucleosomes showed that the enhancement of methylation was limited to nucleosomes bearing uH2B. This work demonstrates a direct biochemical crosstalk between two modifications on separate histone proteins within a nucleosome.
1476-4687 (Electronic) 0028-0836 (Linking) Journal Article Research Support, N.I.H., Extramural
The following values have no corresponding Zotero field: auth-address: Laboratory of Synthetic Protein Chemistry, The Rockefeller University, New York, New York 10065, USA. number: 7196 accession-num: 18449190
Keywords: Animals; Humans; Catalytic Domain; Ubiquitin/*metabolism; Lysine/metabolism; Allosteric Regulation; Histones/chemical synthesis/*metabolism; Methylation; Methyltransferases/genetics/*metabolism; Nucleosomes/chemistry/*metabolism; Xenopus

Peptide ligation via side-chain auxiliary - Lutsky, Marina-Yamit; Nepomniaschiy, Natalia; Brik, Ashraf (Chem. Commun., 2008)
A new peptide ligation strategy based on a side-chain auxiliary was developed; the auxiliary is fairly simple and can be removed, without product isolation, under basic conditions.
1359-7345
The following values have no corresponding Zotero field: number: 10 publisher: The Royal Society of Chemistry

Conformational preferences and pKa Value of cysteine residue - Lee, Joo Yun; Byun, Byung Jin; Kang, Young Kee (J. Chem. Phys. B, 2008)
The following values have no corresponding Zotero field: number: 36 publisher: American Chemical Society

Understanding selenocysteine through conformational analysis, proton affinities, acidities and bond dissociation energies - Kaur, D.; Sharma, P.; Bharatam, P. V.; Kaur, M. (Int. J. Quantum Chem., 2008)
Keywords: #nosource

Chemoselective ligation and modification strategies for peptides and proteins - Hackenberger, C. P.; Schwarzer, D. (Angew. Chem. Int. Ed., 2008)
The investigation of biological processes by chemical methods, commonly referred to as chemical biology, often requires chemical access to biologically relevant macromolecules such as peptides and proteins. Building upon solid-phase peptide synthesis, investigations have focused on the development of chemoselective ligation and modification strategies to link synthetic peptides or other functional units to larger synthetic and biologically relevant macromolecules. This Review summarizes recent developments in the field of chemoselective ligation and modification strategies and illustrates their application, with examples ranging from the total synthesis of proteins to the semisynthesis of naturally modified proteins.
1521-3773 (Electronic) 1433-7851 (Linking) Journal Article Research Support, Non-U.S. Gov't Review
The following values have no corresponding Zotero field: auth-address: Institute for Chemistry and Biochemistry, Freie Universitat Berlin, Takustrasse 3, 14195 Berlin, Germany. hackenbe@chemie.fu-berlin.de number: 52 accession-num: 19072788
Keywords: Peptides/*chemical synthesis/chemistry/genetics; Proteins/*chemical synthesis/chemistry/genetics

Native chemical ligation at valine - Haase, C.; Rohde, H.; Seitz, O. (Angew. Chem. Int. Ed., 2008)
1521-3773 (Electronic) 1433-7851 (Linking) Journal Article
The following values have no corresponding Zotero field: auth-address: Humboldt-Universitat zu Berlin, Institut fur Chemie, Brook-Taylor-Strasse 2, 12489 Berlin, Germany. number: 36 accession-num: 18626881
Keywords: Amino Acid Sequence; Peptides/*chemical synthesis/chemistry; Molecular Sequence Data; Valine/*chemistry; Penicillamine/*chemistry

Rate enhancement of the oxidative folding of lysozyme by the use of aromatic thiol containing redox buffers - Gurbhele-Tupkar, M. C.; Perez, L. R.; Silva, Y.; Lees, W. J. (Bioorg. Med. Chem., 2008)
Almost all therapeutic proteins and most extracellular proteins contain disulfide bonds. The production of these proteins in bacteria or in vitro is challenging due to the need to form the correctly matched disulfide bonds during folding. One important parameter for efficient in vitro folding is the composition of the redox buffer, a mixture of a small molecule thiol and small molecule disulfide. The effects of different redox buffers on protein folding, however, have received limited attention. The oxidative folding of denatured reduced lysozyme was followed in the presence of redox buffers containing varying concentrations of five different aromatic thiols or the traditional aliphatic thiol glutathione (GSH). Aromatic thiols eliminated the lag phase at low disulfide concentrations, increased the folding rate constant up to 11-fold, and improved the yield of active protein relative to GSH. The yield of active protein was similar for four of the five aromatic thiols and for glutathione at pH 7 as well as for glutathione at pH 8.2. At pH 6 the positively charged aromatic thiol provided a higher yield than the negatively charged thiols.
R25 GM061347/GM/NIGMS NIH HHS/United States T34 GM008771/GM/NIGMS NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. England
The following values have no corresponding Zotero field: auth-address: Department of Chemistry and Biochemistry, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA. alt-title: Bioorganic & medicinal chemistry number: 5 accession-num: 18065232
Keywords: Animals; Kinetics; Molecular Structure; *Protein Folding; Sulfhydryl Compounds/*chemistry; Glutathione/chemistry/metabolism; Oxidation-Reduction; Disulfides/chemistry; Buffers; Chickens; Muramidase/*chemistry/*metabolism; Protein Denaturation

Target-catalyzed transfer reactions for the amplified detection of RNA - Grossmann, T. N.; Roglin, L.; Seitz, O. (Angew. Chem. Int. Ed., 2008)
Grossmann, Tom N Roglin, Lars Seitz, Oliver Germany International ed. in English Angew Chem Int Ed Engl. 2008;47(37):7119-22. doi: 10.1002/anie.200801355.
The following values have no corresponding Zotero field: auth-address: Institut fur Chemie der Humboldt-Universitat zu Berlin, Brook-Taylor-Strasse 2, 12489 Berlin, Germany. number: 37 edition: 2008/08/05 accession-num: 18677727
Keywords: Catalysis; Biotin/chemistry; Peptide Nucleic Acids/chemistry; Enzyme-Linked Immunosorbent Assay/*methods; HIV-1/genetics; Molecular Probes/chemistry; Polymerase Chain Reaction; RNA/*analysis; Sensitivity and Specificity

Is ascorbate able to reduce disulfide bridges? A cautionary note - Giustarini, D.; Dalle-Donne, I.; Colombo, R.; Milzani, A.; Rossi, R. (Nitric Oxide, 2008)
The biotin switch assay has recently been proposed as the eligible method to identify different S-nitrosated proteins in biological matrices. However, notwithstanding its wide application, a thorough validation of this method is still lacking. In particular, it has been suggested that ascorbate concentrations higher than 1mM (as proposed in the original method) are needed since ascorbate reaction with S-nitrosothiols is slow. But the selectivity of ascorbate as a cleaving agent of the S-N bond under these conditions has not been well characterized. Our data indicate that ascorbate is able to reduce disulfide bridges of DTNB, cystine, cystinylglycine, glutathione disulfide, protein mixed disulfides and biotin-HPDP with pH and concentration dependent rates. Additionally, we tested the effect of indirect sunlight on ascorbate-mediated cleavage of both disulfides and S-nitrosothiols.
Journal Article United States biology and chemistry / official journal of the Nitric Oxide Society
The following values have no corresponding Zotero field: auth-address: Department of Evolutionary Biology, Laboratory of Pharmacology and Toxicology, University of Siena, via A. Moro 4, I-53100 Siena, Italy. number: 3 accession-num: 18675931
Keywords: Animals; Hydrogen-Ion Concentration; Chromatography, High Pressure Liquid; Oxidation-Reduction; Disulfides/*chemistry; Ascorbic Acid/*chemistry; Dipeptides/chemistry; Bicyclo Compounds/chemistry; Biotin/analogs & derivatives/chemistry; Cystine/chemistry; Dithionitrobenzoic Acid/chemistry; Glutathione Disulfide/chemistry; Rats; S-Nitrosothiols/chemistry; Serum Albumin, Bovine/chemistry/pharmacology; Sunlight

Cyclic peptide inhibitors of staphylococcal virulence prepared by Fmoc-based thiolactone peptide synthesis - George, Elizabeth A.; Novick, Richard P.; Muir, Tom W. (J. Am. Chem. Soc., 2008)
Virulence factor production in Staphylococcus aureus is largely under the control of the accessory gene regulator (agr) quorum sensing system. There are four agr groups, all of which exhibit bacterial interference: each agr type synthesizes a cyclic autoinducing peptide (AIP) with a distinct sequence that activates its cognate AgrC receptor and inhibits activation of others. To better understand inhibitory AIP−AgrC interactions, we aimed to identify the minimal molecular determinants required to inhibit both non-cognate and cognate receptors. This minimization of the AIP pharmacophore also may have therapeutic relevance as the use of native AIPs to block virulence of non-cognate agr strains can prevent the establishment of an infection in vivo. We synthesized and evaluated the inhibitory activities of 10 AIP derivatives based on a truncated AIP analogue that inhibits all four agr types. To carry out the rapid, parallel synthesis of these peptides, we employed a new linker for Fmoc-based thioester peptide synthesis. Our results identify key structural elements that are necessary for AgrC inhibition and reveal key differences between non-cognate and cognate inhibitory requirements. Virulence factor production in Staphylococcus aureus is largely under the control of the accessory gene regulator (agr) quorum sensing system. There are four agr groups, all of which exhibit bacterial interference: each agr type synthesizes a cyclic autoinducing peptide (AIP) with a distinct sequence that activates its cognate AgrC receptor and inhibits activation of others. To better understand inhibitory AIP−AgrC interactions, we aimed to identify the minimal molecular determinants required to inhibit both non-cognate and cognate receptors. This minimization of the AIP pharmacophore also may have therapeutic relevance as the use of native AIPs to block virulence of non-cognate agr strains can prevent the establishment of an infection in vivo. We synthesized and evaluated the inhibitory activities of 10 AIP derivatives based on a truncated AIP analogue that inhibits all four agr types. To carry out the rapid, parallel synthesis of these peptides, we employed a new linker for Fmoc-based thioester peptide synthesis. Our results identify key structural elements that are necessary for AgrC inhibition and reveal key differences between non-cognate and cognate inhibitory requirements.
doi: 10.1021/ja711126e 0002-7863 doi: 10.1021/ja711126e
The following values have no corresponding Zotero field: number: 14 publisher: American Chemical Society

Caspase cleavage of the MET receptor generates an HGF interfering fragment - Deheuninck, J.; Foveau, B.; Goormachtigh, G.; Leroy, C.; Ji, Z.; Tulasne, D.; Fafeur, V. (Biochem. Biophys. Res. Commun., 2008)
The MET tyrosine kinase receptor activated by its ligand HGF/SF, induces several cellular responses, including survival. Nonetheless, the MET receptor is cleaved in stress conditions by caspases within its intracellular region, generating a 40kDa fragment, p40 MET, with pro-apoptotic properties. Here, we established that this cleavage splits the receptor at the juxtamembrane ESVD site, causing the concomitant generation of p100 MET, corresponding to the entire extracellular region of the MET receptor still spanning the membrane. This fragment is able to bind HGF/SF and to prevent HGF-dependent signaling downstream of full MET, demonstrating its function as a decoy receptor.
1090-2104 (Electronic) 0006-291X (Linking) Journal Article Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: UMR-8161, Institut de Biologie de Lille, CNRS, Universite de Lille-1, Universite de Lille-2, Institut Pasteur de Lille, BP 447, F-59021 Lille Cedex, France. number: 3 accession-num: 18187039
Keywords: Animals; Humans; Cells, Cultured; Dogs; Apoptosis/drug effects; Caspases/*metabolism; Cell Fractionation; Gene Transfer Techniques; Hepatocyte Growth Factor/antagonists & inhibitors/chemistry/*metabolism; Peptide Fragments/*biosynthesis/genetics/pharmacology; Proto-Oncogene Proteins c-met/chemistry/genetics/*metabolism; Signal Transduction/drug effects; TNF-Related Apoptosis-Inducing Ligand/pharmacology

Native chemical ligation at valine: a contribution to peptide and glycopeptide synthesis - Chen, J.; Wan, Q.; Yuan, Y.; Zhu, J.; Danishefsky, S. J. (Angew. Chem. Int. Ed., 2008)
1521-3773 (Electronic) 1433-7851 (Linking) Journal Article Research Support, N.I.H., Extramural
The following values have no corresponding Zotero field: auth-address: Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, NY 10065, USA. number: 44 accession-num: 18833563
Keywords: Valine/*chemistry; Glycopeptides/*chemical synthesis/chemistry

Amino acid composition and protein dimension - Carugo, O. (Protein Sci., 2008)
There is indirect evidence that the amino acid composition of proteins depends on their dimension. The amino acid composition of a nonredundant set of about 550,000 proteins was determined and it was observed that, in the range of 50-200 residues, the percentage of occurrence of most of the residue types significantly depends on protein dimension. This result should prove useful in analyzing protein sequences and genomics.
Journal Article Research Support, Non-U.S. Gov't United States a publication of the Protein Society
The following values have no corresponding Zotero field: auth-address: Department of General Chemistry, Pavia University, I-27100 Pavia, Italy. oliviero.carugo@univie.ac.at number: 12 accession-num: 18780815
Keywords: Protein Conformation; Proteins/*chemistry/metabolism; Computer Simulation; Algorithms; Amino Acids/*analysis; Computational Biology/methods; Databases, Protein

Orthogonal ligation: a three piece assembly of a PNA-peptide-PNA conjugate - Burlina, F.; Dixson, D. D.; Doyle, R. P.; Chassaing, G.; Boddy, C. N.; Dawson, P.; Offer, J. (Chem. Commun., 2008)
A PNA-peptide-PNA conjugate was assembled from three fragments using a combination of native chemical ligation and an orthogonal, auxiliary-mediated ligation.
Burlina, Fabienne Dixson, David D Doyle, Robert P Chassaing, Gerard Boddy, Christopher N Dawson, Philip Offer, John England Cambridge, England Chem Commun (Camb). 2008 Jun 28;(24):2785-7. doi: 10.1039/b801242c. Epub 2008 Apr 14.
The following values have no corresponding Zotero field: auth-address: UPMC Univ Paris 06, CNRS UMR 7613, 4 place Jussieu, F-75005 Paris, France. fabienne.burlina@upmc.fr number: 24 edition: 2008/08/09 accession-num: 18688310 work-type: Research Support, Non-U.S. Gov't
Keywords: Amino Acid Sequence; Peptides/*chemistry; Molecular Sequence Data; Chromatography, High Pressure Liquid; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Models, Chemical; Peptide Nucleic Acids/*chemical synthesis

Total synthesis by modern chemical ligation methods and high resolution (1.1 Å) X-ray structure of ribonuclease A - Boerema, David J.; Tereshko, Valentina A.; Kent, Stephen B. H. (Pept. Sci., 2008)
The total chemical synthesis of RNase A using modern chemical ligation methods is described, illustrating the significant advances that have been made in chemical protein synthesis since Gutte and Merrifield's pioneering preparation of RNase A in 1969. The identity of the synthetic product was confirmed through rigorous characterization, including the determination of the X-ray crystal structure to 1.1 Angstrom resolution. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90:278–286, 2008. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
1097-0282
The following values have no corresponding Zotero field: number: 3 publisher: Wiley Subscription Services, Inc., A Wiley Company
Keywords: native chemical ligation; solid phase peptide synthesis; ribonuclease A; total chemical synthesis; X-ray structure

An efficient Fmoc-SPPS approach for the generation of thioester peptide precursors for use in native chemical ligation - Blanco-Canosa, J. B.; Dawson, P. E. (Angew. Chem. Int. Ed., 2008)
1521-3773 (Electronic) 1433-7851 (Linking) Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Departments of Chemistry and Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-7319 http://www.scripps.edu/cb/dawson/ number: 36 accession-num: 18651678
Keywords: Amino Acid Sequence; Peptides/*chemical synthesis; Fluorenes/*chemistry; Esters/chemical synthesis; Sulfur Compounds/chemical synthesis

Thiocarbamate-linked peptides by chemoselective peptide ligation - Besret, S.; Ollivier, N.; Blanpain, A.; Melnyk, O. (J. Pept. Sci., 2008)
Peptide chemical ligation chemistries, which allow the chemoselective coupling of unprotected peptide fragments, are useful tools for synthesizing native polypeptides or unnatural peptide-based macromolecules. We show here that the phenylthiocarbonyl group can be easily introduced into peptides on alpha or epsilon amino groups using phenylthiochloroformate and standard solid-phase method. It reacts chemoselectively with cysteinyl peptides to give an alkylthiocarbamate bond. S,N-shift of the alkylaminocarbonyl group from the Cys side chain to the alpha-amino group did not occur. The method was used for linking two peptide chains through their N-termini, for the synthesis of a cyclic peptide or for the synthesis of di- or tetravalent multiple antigenic peptides (MAPs). Thiocarbamate ligation is thus complementary to thioether, thioester or disulfide ligation methods.
Journal Article Research Support, Non-U.S. Gov't England an official publication of the European Peptide Society
The following values have no corresponding Zotero field: auth-address: UMR 8161 CNRS-Universite de Lille 1 et 2, Institut Pasteur de Lille, IFR 142, 1 rue du Pr Calmette, 59021, Lille, France. number: 12 accession-num: 18752254
Keywords: Cysteine/chemistry; Peptides/*chemistry; Molecular Structure; Thiocarbamates/*chemistry

Sugar-assisted glycopeptide ligation with complex oligosaccharides: scope and limitations - Bennett, C. S.; Dean, S. M.; Payne, R. J.; Ficht, S.; Brik, A.; Wong, C. H. (J. Am. Chem. Soc., 2008)
We have previously shown sugar-assisted ligation (SAL) to be a useful method for the convergent construction of glycopeptides. However to date SAL has only been carried out on systems where the thiol auxiliary is attached to a monosaccharide. For SAL to be truly applicable to the construction of fully elaborated glycopeptides and glycoproteins, it must be possible to carry out the reaction when the thiol auxiliary is attached to more elaborate sugars, as these are frequently what are observed in nature. Here we examine the effects of glycosylation at C-3, C-4, and C-6 of the C-2 auxiliary-containing glycan. Model glycopeptides where synthesized chemoenzymatically and reacted with peptide thioesters used in our previous work. These studies reveal that SAL is sensitive to extended glycosylation on the auxiliary-containing sugar. While it is possible to carry out SAL with extended glycosylation at C-4 and C-6, the presence of glycosylation at C-3 prevents the ligation from occurring. Additionally, with glycosylation at C-4 the ligation efficiency is affected by the identity of the N-terminal AA, while the nature of the C-terminal residue of the peptide thioester does not appear to affect ligation efficiency. These studies provide useful guidelines in deciding when it is appropriate to use SAL in the synthesis of complex glycopeptides and glycoproteins and how to choose ligation junctions for optimal yield.
R37 GM044154/GM/NIGMS NIH HHS/United States R37 GM044154-19/GM/NIGMS NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. alt-title: Journal of the American Chemical Society number: 36 accession-num: 18698778
Keywords: Glycosylation; Amino Acids/chemical synthesis/chemistry; Sulfhydryl Compounds/chemistry; Glycopeptides/*chemical synthesis; Acetylgalactosamine/chemistry; Acetylglucosamine/chemistry; Glycosyltransferases/chemistry; Oligosaccharides/*chemistry; Polysaccharides/chemistry

A high affinity hepatocyte growth factor-binding site in the immunoglobulin-like region of Met - Basilico, C.; Arnesano, A.; Galluzzo, M.; Comoglio, P. M.; Michieli, P. (J. Biol. Chem., 2008)
Hepatocyte growth factor (HGF) and its high affinity receptor, the tyrosine kinase Met, play a key role in embryo development and tumor invasion. Both HGF and Met are established targets for cancer therapy. However, the mechanism of their interaction is complex and remains elusive. HGF is secreted as a monomeric precursor (pro-HGF) that binds to but does not activate Met. Mature HGF is a alpha/beta heterodimer containing a high affinity Met-binding site in the alpha-chain (HGF-alpha) and a low affinity Met-binding site in the beta-chain (HGF-beta). The extracellular portion of Met contains a semaphorin (Sema) domain, a cysteine-rich hinge (plexin-semaphorin-integrin), and four immunoglobulin-like domains (immunoglobulin-like regions in plexins and transcription factors (IPT) 1-4). HGF-beta binds to Sema through a low affinity contact. The domain of Met responsible for high affinity binding to HGF-alpha has not been identified yet. Here we show that this long sought after binding site lies in the immunoglobulin-like region of Met and more precisely in IPT 3 and 4. We also show that IPT 3 and 4 are sufficient to transmit the signal for kinase activation to the cytoplasm, although the lack of Sema makes the receptor equally sensitive to mature HGF and pro-HGF. Finally, we provide evidence that soluble Met-derived proteins containing either the low affinity or high affinity HGF-binding site antagonize HGF-induced invasive growth both in vitro and in xenografts. These data suggest that the immunoglobulin-like region of Met cooperates with the Sema domain in binding to HGF and in controlling Met kinase activity. Although the IPT-HGF-alpha interaction provides binding strength, the Sema-HGF-beta contact confers selective sensitivity to the active form of the ligand.
0021-9258 (Print) 0021-9258 (Linking) Journal Article Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Division of Molecular Oncology, Institute for Cancer Research and Treatment, University of Turin Medical School, I-10060 Candiolo, Turin, Italy. number: 30 accession-num: 18495663
Keywords: Animals; Humans; Protein Binding; Mice; Protein Structure, Tertiary; Binding Sites; Cell Line, Tumor; Antineoplastic Agents/pharmacology; Collagen/chemistry; Hepatocyte Growth Factor/*chemistry/metabolism; Immunoglobulins/*chemistry; Neoplasm Metastasis; Neoplasm Transplantation; Protein Engineering/methods; Proto-Oncogene Proteins c-met/*chemistry/metabolism

Sugar-assisted ligation in glycoprotein synthesis - Yang, Y. Y.; Ficht, S.; Brik, A.; Wong, C. H. (J. Am. Chem. Soc., 2007)
Sugar-assisted ligation (SAL) presents an attractive strategy for the synthesis of glycopeptides, including the synthesis of cysteine-free beta-O-linked and N-linked glycopeptides. Here we extended the utility of SAL for the synthesis of alpha-O-linked glycopeptides and glycoproteins. In order to explore SAL in the context of glycoprotein synthesis, we developed a new chemical synthetic route for the alpha-O-linked glycoprotein diptericin epsilon. In the first stage of our synthesis, diptericin segment Cys(Acm)37-Gly(52) and segment Val(53)-Phe(82) were assembled by SAL through a Gly-Val ligation junction. Subsequently, after Acm deprotection, diptericin segment Cys(37)-Phe(82) was ligated to segment Asp(1)-Asn(36) by means of native chemical ligation (NCL) to give the full sequence of diptericin epsilon. In the final synthetic step, hydrogenolysis was applied to remove the thiol handle from the sugar moiety with the concomitant conversion of mutated Cys(37) into the native alanine residue. In addition, we extended the applicability of SAL to the synthesis of glycopeptides containing cysteine residues by carrying out selective desulfurization of the sulfhydryl-modified sugar moiety in the presence of acetamidomethyl (Acm) protected cysteine residues. The results presented here demonstrated for the first time that SAL could be a general and useful tool in the chemical synthesis of glycoproteins.
GM044154-17/GM/NIGMS NIH HHS/United States R37 GM044154/GM/NIGMS NIH HHS/United States R37 GM044154-17/GM/NIGMS NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. alt-title: Journal of the American Chemical Society number: 24 accession-num: 17523644
Keywords: Protein Conformation; Carbohydrate Conformation; Carbohydrates/*chemistry; Glycoproteins/*chemical synthesis

Free-radical-based, specific desulfurization of cysteine: a powerful advance in the synthesis of polypeptides and glycopolypeptides - Wan, Q.; Danishefsky, S. J. (Angew. Chem. Int. Ed., 2007)
The following values have no corresponding Zotero field: auth-address: Laboratory of Bioorganic Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. number: 48 edition: 2007/11/30 accession-num: 18046687
Wan, Qian Danishefsky, Samuel J CA02848/CA/NCI NIH HHS/United States CA28824/CA/NCI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Germany Angewandte Chemie (International ed. in English) Angew Chem Int Ed Engl. 2007;46(48):9248-52.
Keywords: Cysteine/*chemistry; Sulfur/chemistry; Peptides/*chemical synthesis; Glycopeptides/*chemical synthesis; Free Radicals/chemistry

Convergent chemical synthesis and crystal structure of a 203 amino acid “covalent dimer” HIV-1 protease enzyme molecule - Torbeev, Vladimi Yu; Kent, Stephen B. H. (Angew. Chem. Int. Ed., 2007)
1521-3773
The following values have no corresponding Zotero field: number: 10 publisher: WILEY-VCH Verlag
Keywords: native chemical ligation; peptides; protein synthesis; convergent synthesis; enzymes

Peptide dithiodiethanol esters for in situ generation of thioesters for use in native ligation - Tofteng, A. Pernille; Jensen, Knud J.; Hoeg-Jensen, Thomas (Tetrahedron Lett., 2007)
A new approach is described for the general Fmoc-based solid-phase synthesis of C-terminal peptide (thio)esters. One hydroxy group of 2,2-dithiodiethanol (used in large excess) was anchored on trityl resin, and the remaining hydroxy group was loaded with the first amino acid. Standard chain elongation and TFA-based peptide release yielded peptide C-terminal dithiodiethanol esters in good purities. Under standard conditions of native chemical ligation (excess thiol, neutral pH), the dithiodiethanol function is presumably reduced and rearranged (or equilibrated) to the thioester via a 5-membered intermediate. The resulting thioesters are shown to undergo native chemical ligation with N-terminal cysteine peptides. Notably, hydrolysis of the reduced ester is a major competing reaction, especially in the presence of 6 M guanidinium chloride, which is often required for solubilization of large peptide fragments.
The following values have no corresponding Zotero field: number: 12
Keywords: Native chemical ligation; Hydrolysis; Peptide thioester; Dithiodiethanol linker

UniRef: comprehensive and non-redundant UniProt reference clusters - Suzek, B. E.; Huang, H.; McGarvey, P.; Mazumder, R.; Wu, C. H. (Bioinformatics, 2007)
MOTIVATION: Redundant protein sequences in biological databases hinder sequence similarity searches and make interpretation of search results difficult. Clustering of protein sequence space based on sequence similarity helps organize all sequences into manageable datasets and reduces sampling bias and overrepresentation of sequences. RESULTS: The UniRef (UniProt Reference Clusters) provide clustered sets of sequences from the UniProt Knowledgebase (UniProtKB) and selected UniProt Archive records to obtain complete coverage of sequence space at several resolutions while hiding redundant sequences. Currently covering >4 million source sequences, the UniRef100 database combines identical sequences and subfragments from any source organism into a single UniRef entry. UniRef90 and UniRef50 are built by clustering UniRef100 sequences at the 90 or 50% sequence identity levels. UniRef100, UniRef90 and UniRef50 yield a database size reduction of approximately 10, 40 and 70%, respectively, from the source sequence set. The reduced redundancy increases the speed of similarity searches and improves detection of distant relationships. UniRef entries contain summary cluster and membership information, including the sequence of a representative protein, member count and common taxonomy of the cluster, the accession numbers of all the merged entries and links to rich functional annotation in UniProtKB to facilitate biological discovery. UniRef has already been applied to broad research areas ranging from genome annotation to proteomics data analysis. AVAILABILITY: UniRef is updated biweekly and is available for online search and retrieval at http://www.uniprot.org, as well as for download at ftp://ftp.uniprot.org/pub/databases/uniprot/uniref. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
The following values have no corresponding Zotero field: auth-address: Protein Information Resource, Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC 20007, USA. bes23@georgetown.edu alt-title: Bioinformatics (Oxford, England) number: 10 accession-num: 17379688
U41 HG007822/HG/NHGRI NIH HHS/United States U01 HG02712/HG/NHGRI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural England
Keywords: Amino Acid Sequence; Animals; Humans; Proteins/*chemistry; *Databases, Protein; *Computational Biology; Information Storage and Retrieval

Development of O-acyl isopeptide method - Sohma, Y.; Yoshiya, T.; Taniguchi, A.; Kimura, T.; Hayashi, Y.; Kiso, Y. (Biopolymers, 2007)
The following values have no corresponding Zotero field: auth-address: Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, 21st Century COE Program, Kyoto Pharmaceutical University, Kyoto, Japan. alt-title: Biopolymers number: 2 accession-num: 17236207
Keywords: Amino Acid Sequence; Molecular Structure; Peptides/*chemical synthesis/chemistry; Molecular Sequence Data; Acylation; Methods; Amyloid beta-Peptides/chemical synthesis/chemistry; Peptide Fragments/chemical synthesis/chemistry

Self-assembled templates for polypeptide synthesis - Ryadnov, Maxim G.; Woolfson, Derek N. (J. Am. Chem. Soc., 2007)
doi: 10.1021/ja072960s 0002-7863 doi: 10.1021/ja072960s
The following values have no corresponding Zotero field: number: 45 publisher: American Chemical Society

Selective desulfurization of cysteine in the presence of Cys(Acm) in polypeptides obtained by native chemical ligation - Pentelute, B. L.; Kent, S. B. H. (Org. Lett., 2007)
Increased versatility for the synthesis of proteins and peptides by native chemical ligation requires the ability to ligate at positions other than Cys. Here, we report that Raney nickel can be used under standard conditions for the selective desulfurization of Cys in the presence of Cys(Acm). This simple and practical tactic enables the more common Xaa-Ala junctions to be used as ligation sites for the chemical synthesis of Cys-containing peptides and proteins. [reaction: see text].
Journal Article Research Support, U.S. Gov't, Non-P.H.S. United States
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Institute for Biophysical Dynamics, Gordon Center for Integrative Science, The University of Chicago, Chicago Illinois 60637, USA. alt-title: Organic letters number: 4 accession-num: 17286375
Keywords: Amino Acid Sequence; Models, Molecular; Molecular Sequence Data; Sulfur/*chemistry; Peptides/*chemical synthesis; Spectrometry, Mass, Electrospray Ionization; Amyloid/chemical synthesis; Cysteine/*analogs & derivatives/*chemistry; Islet Amyloid Polypeptide

Extended sugar-assisted glycopeptide ligations: development, scope, and applications - Payne, R. J.; Ficht, S.; Tang, S.; Brik, A.; Yang, Y. Y.; Case, D. A.; Wong, C. H. (J Am Chem Soc, 2007)
Recently, we reported the development of sugar-assisted ligation (SAL), a novel peptide ligation method for the synthesis of glycopeptides. After screening a large number of glycoprotein sequences in a glycoprotein database, it became evident that a large proportion (approximately 53%) of O-glycosylation sites contain amino acid residues that will not undergo SAL reactions. To overcome these inherent limitations and broaden the scope of the method we report here the development of an extended SAL method. Glycopeptides containing up to six amino acid extensions N-terminal to the glycosylated residue were shown to facilitate ligation reactions with peptide thioesters, and these products were isolated in good yields. Kinetic analysis was used to show that as glycopeptides were extended by further amino acid residues, ligation reactions became slower. This finding was rationalized by molecular dynamics simulations using AMBER9. These studies suggested a general trend whereby the proximal distance between the reactive sites of the thioester intermediate (the N-terminal amine and the carbonyl carbon of the thioester) increased as glycopeptides were extended, thus slowing down the ligation rate. Each of the extended SAL methods showed broad tolerance to a number of different amino acid combinations at the ligation junction. Re-evaluation of the glycoprotein database suggested that 95% of the O-linked glycosylation sites can now be utilized to facilitate SAL or extended SAL reactions. As such, this method represents an extremely valuable tool for the synthesis of naturally occurring glycopeptides and glycoproteins. To demonstrate the applicability of the method, extended SAL was successfully implemented in the synthesis of the starting unit of the cancer-associated MUC1 glycoprotein.
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: Departments of Chemistry and Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. alt-title: Journal of the American Chemical Society number: 44 accession-num: 17935327
Keywords: Kinetics; Esters/chemistry; Amino Acids/chemistry; Glycosylation; Models, Chemical; Glycopeptides/*chemical synthesis/chemistry; Carbohydrate Conformation; Carbohydrates/*chemistry

Interactions between hydrophobic and ionic solutes in aqueous guanidinium chloride and urea solutions: Lessons for protein denaturation mechanism - O'Brien, Edward P.; Dima, Ruxandra I.; Brooks, Bernard; Thirumalai, D. (J. Am. Chem. Soc., 2007)
doi: 10.1021/ja069232+ 0002-7863 doi: 10.1021/ja069232+
The following values have no corresponding Zotero field: number: 23 publisher: American Chemical Society

The use of differential scanning fluorimetry to detect ligand interactions that promote protein stability - Niesen, F. H.; Berglund, H.; Vedadi, M. (Nat. Protoc., 2007)
Differential scanning fluorimetry (DSF) is a rapid and inexpensive screening method to identify low-molecular-weight ligands that bind and stabilize purified proteins. The temperature at which a protein unfolds is measured by an increase in the fluorescence of a dye with affinity for hydrophobic parts of the protein, which are exposed as the protein unfolds. A simple fitting procedure allows quick calculation of the transition midpoint; the difference in the temperature of this midpoint in the presence and absence of ligand is related to the binding affinity of the small molecule, which can be a low-molecular-weight compound, a peptide or a nucleic acid. DSF is best performed using a conventional real-time PCR instrument. Ligand solutions from a storage plate are added to a solution of protein and dye, distributed into the wells of the PCR plate and fluorescence intensity measured as the temperature is raised gradually. Results can be obtained in a single day.
Journal Article Research Support, Non-U.S. Gov't England
The following values have no corresponding Zotero field: auth-address: Structural Genomics Consortium, Botnar Research Centre, Oxford University, Oxford, UK. frank.niesen@sgc.ox.ac.uk alt-title: Nature protocols number: 9 accession-num: 17853878
Keywords: Animals; Enzyme Stability; Temperature; Protein Folding; Ligands; *Protein Conformation; Polymerase Chain Reaction; *Protein Denaturation; Citrate (si)-Synthase/chemistry/metabolism; Fluorescent Dyes/analysis; Fluorometry/*methods; Oxaloacetic Acid/metabolism; Swine/metabolism

Antitumor activity, X-ray crystal structure, and DNA binding properties of thiocoraline A, a natural bisintercalating thiodepsipeptide - Negri, A.; Marco, E.; Garcia-Hernandez, V.; Domingo, A.; Llamas-Saiz, A. L.; Porto-Sanda, S.; Riguera, R.; Laine, W.; David-Cordonnier, M. H.; Bailly, C.; Garcia-Fernandez, L. F.; Vaquero, J. J.; et al. (J. Med. Chem., 2007)
The marine natural product thiocoraline A displayed approximately equal cytotoxic activity at nanomolar concentrations in a panel of 12 human cancer cell lines. X-ray diffraction analyses of orthorhombic crystals of this DNA-binding drug revealed arrays of docked pairs of staple-shaped molecules in which one pendent hydroxyquinoline chromophore from each cysteine-rich molecule appears intercalated between the two chromophores of a facing molecule. This arrangement is in contrast to the proposed mode of binding to DNA that shows the two drug chromophores clamping two stacked base pairs, in agreement with the nearest-neighbor exclusion principle. Proof of DNA sequence recognition was obtained from both classical DNase I footprinting experiments and determination of the melting temperatures of several custom-designed fluorescently labeled oligonucleotides. A rationale for the DNA-binding behavior was gained when models of thiocoraline clamping a central step embedded in several octanucleotides were built and studied by means of unrestrained molecular dynamics simulations in aqueous solution.
Negri, Ana Marco, Esther Garcia-Hernandez, Veronica Domingo, Alberto Llamas-Saiz, Antonio L Porto-Sanda, Silvia Riguera, Ricardo Laine, William David-Cordonnier, Marie-Helene Bailly, Christian Garcia-Fernandez, Luis F Vaquero, Juan Jose Gago, Federico J Med Chem. 2007 Jul 12;50(14):3322-33. Epub 2007 Jun 16.
The following values have no corresponding Zotero field: auth-address: Departamento de Farmacologia, Universidad de AlcalA, E-28871 Madrid, Spain. alt-title: Journal of medicinal chemistry number: 14 edition: 2007/06/19 accession-num: 17571868 work-type: Research Support, Non-U.S. Gov't
Keywords: Humans; Stereoisomerism; Base Sequence; Crystallography, X-Ray; Cell Line, Tumor; DNA/*metabolism; Antineoplastic Agents/chemistry/metabolism/*pharmacology; Depsipeptides/chemistry/metabolism/*pharmacology; DNA Footprinting

Peptide thioester synthesis via an auxiliary-mediated N–S acyl shift reaction in solution - Nakamura, K.; Mori, H.; Kawakami, T.; Hojo, H.; Nakahara, Y.; Aimoto, S. (Int. J. Pep. Res. Therap., 2007)
Keywords: #nosource

Solid-phase synthesis of peptide thioesters with self-purification - Mende, F.; Seitz, O. (Angew. Chem. Int. Ed., 2007)
Mende, Franziska Seitz, Oliver Germany International ed. in English Angew Chem Int Ed Engl. 2007;46(24):4577-80.
The following values have no corresponding Zotero field: auth-address: Humboldt-Universitat zu Berlin, Institut fur Chemie, Brook-Taylor-Strasse 2, 12489 Berlin, Germany. number: 24 edition: 2007/05/05 accession-num: 17477337
Keywords: Amino Acid Sequence; Chromatography, High Pressure Liquid; Esters; Cyclization; Methods; Peptides/*chemical synthesis; Sulfur Compounds/*chemical synthesis

Benchmarking and validating algorithms that estimate pK a values of drugs based on their molecular structures - Meloun, Milan; BordovskÃ¡, Sylva (Anal. Bioanal. Chem., 2007)
Anal Bioanal Chem 1618-2642
The following values have no corresponding Zotero field: number: 4 publisher: Springer-Verlag
Keywords: Dissociation constants; Goodness-of-fit; Influential points; Outliers; pK a accuracy; pK a prediction; Residuals; Williams graph

Experimental and theoretical study of the photodissociation reaction of thiophenol at 243 nm: Intramolecular orbital alignment of the phenylthiyl radical - Lim, Ivan S.; Lim, Jeong Sik; Lee, Yoon Sup; Kim, Sang Kyu (J. Phys. Chem., 2007)
The following values have no corresponding Zotero field: number: 3
Keywords: photochemistry; ab initio calculations; bonds (chemical); excited states; free radical reactions; ground states; molecule-photon collisions; nonradiative transitions; organic compounds; photodissociation; potential energy surfaces; reaction kinetics theory; spectrochemical analysis

In silico prediction of ionization constants of drugs - Lee, P. H.; Ayyampalayam, S. N.; Carreira, L. A.; Shalaeva, M.; Bhattachar, S.; Coselmon, R.; Poole, S.; Gifford, E.; Lombardo, F. (Mol. Pharm., 2007)
Most pharmacologically active molecules contain one or more ionizing groups, and it is well-known that knowledge of the ionization state of a drug, indicated by the pKa value, is critical for understanding many properties important to the drug discovery and development process. The ionization state of a compound directly influences such important pharmaceutical characteristics as aqueous solubility, permeability, crystal structure, etc. Tremendous advances have been made in the field of experimental determination of pKa, in terms of both quantity/speed and quality/accuracy. However, there still remains a need for accurate in silico predictions of pKa both to estimate this parameter for virtual compounds and to focus screening efforts of real compounds. The computer program SPARC (SPARC Performs Automated Reasoning in Chemistry) was used to predict the ionization state of a drug. This program has been developed based on the solid physical chemistry of reactivity models and applied to successfully predict numerous physical properties as well as chemical reactivity parameters. SPARC predicts both macroscopic and microscopic pKa values strictly from molecular structure. In this paper, we describe the details of the SPARC reactivity computational methods and its performance on predicting the pKa values of known drugs as well as Pfizer internal discovery/development compounds. A high correlation (r2=0.92) between experimental and the SPARC calculated pKa values was obtained with root-mean-square error (RMSE) of 0.78 log unit for a set of 123 compounds including many known drugs. For a set of 537 compounds from the Pfizer internal dataset, correlation coefficient r2=0.80 and RMSE=1.05 were obtained.
1543-8384 (Print) 1543-8384 (Linking) Journal Article
The following values have no corresponding Zotero field: auth-address: Computer Assisted Drug Discovery, Research Formulation, Pharmaceutical Science, Chemical Technology, Lead Discovery Group, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, Michigan 48105, USA. pilhlee@gmail.com number: 4 accession-num: 17629304
Keywords: Stereoisomerism; *Software; Molecular Structure; Hydrogen Bonding; Thermodynamics; Models, Chemical; Static Electricity; *Computer Simulation; Electrophoresis, Capillary; Ions/*chemistry; Pharmaceutical Preparations/*chemistry

Sequential peptide ligation by using a controlled cysteinyl prolyl ester (CPE) autoactivating unit - Kawakami, T.; Aimoto, S. (Tetrahedron Lett., 2007)
A peptide building block containing a cysteinyl prolyl ester (CPE) autoactivating unit was ligated with a cysteinyl peptide under native chemical ligation conditions. The CPE autoactivating function can be controlled by the protection of the thiol group, permitting the selective ligation of the peptide building block at either the C or N terminus.
11
The following values have no corresponding Zotero field: publisher: Elsevier
Keywords: Peptide thioester; Controlled sequential ligation; CPE autoactivating unit; Peptide ligation; #nosource

Peptide ligation using a building block having a cysteinyl prolyl ester (CPE) autoactivating unit at the carboxy terminus - Kawakami, T.; Aimoto, S. (Chem. Lett., 2007)
Keywords: #nosource

Modular total chemical synthesis of a human immunodeficiency virus type 1 protease - Johnson, Erik C. B.; Malito, Enrico; Shen, Yuequan; Rich, Dan; Tang, Wei-Jen; Kent, Stephen B. H. (J. Am. Chem. Soc., 2014)
doi: 10.1021/ja072870n
The following values have no corresponding Zotero field: number: 37 publisher: American Chemical Society

Towards the total chemical synthesis of integral membrane proteins: a general method for the synthesis of hydrophobic peptide-athioester building blocks - Johnson, Erik C. B.; Kent, Stephen B. H. (Tetrahedron Lett., 2007)
Modification of a peptide-Î±thioester with a sequence of six arginines on the thioester leaving group can render soluble all peptides derived from a polytopic integral membrane protein. This strategy greatly simplifies the synthesis of peptide-Î±thioester building blocks for the total chemical synthesis of integral membrane proteins by native chemical ligation.
The following values have no corresponding Zotero field: number: 10
Keywords: Native chemical ligation; Thioester; Chemical protein synthesis; Diacylglycerol kinase; Integral membrane proteins

Insights from atomic-resolution X-ray structures of chemically synthesized HIV-1 protease in complex with inhibitors - Johnson, E. C.; Malito, E.; Shen, Y.; Pentelute, B.; Rich, D.; Florian, J.; Tang, W. J.; Kent, S. B. H. (J. Mol. Biol., 2007)
The human immunodeficiency virus 1 (HIV-1) protease (PR) is an aspartyl protease essential for HIV-1 viral infectivity. HIV-1 PR has one catalytic site formed by the homodimeric enzyme. We chemically synthesized fully active HIV-1 PR using modern ligation methods. When complexed with the classic substrate-derived inhibitors JG-365 and MVT-101, the synthetic HIV-1 PR formed crystals that diffracted to 1.04- and 1.2-A resolution, respectively. These atomic-resolution structures revealed additional structural details of the HIV-1 PR's interactions with its active site ligands. Heptapeptide inhibitor JG-365, which has a hydroxyethylamine moiety in place of the scissile bond, binds in two equivalent antiparallel orientations within the catalytic groove, whereas the reduced isostere hexapeptide MVT-101 binds in a single orientation. When JG-365 was converted into the natural peptide substrate for molecular dynamic simulations, we found putative catalytically competent reactant states for both lytic water and direct nucleophilic attack mechanisms. Moreover, free energy perturbation calculations indicated that the insertion of catalytic water into the catalytic site is an energetically favorable process.
T32 HD007009/HD/NICHD NIH HHS/United States R01 GM081539/GM/NIGMS NIH HHS/United States R01 GM062548/GM/NIGMS NIH HHS/United States GM62548/GM/NIGMS NIH HHS/United States R01 GM062548-06/GM/NIGMS NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. England
The following values have no corresponding Zotero field: auth-address: Department of Biochemistry and Molecular Biology, The University of Chicago, IL 60637, USA. alt-title: Journal of molecular biology number: 3 accession-num: 17869270
Keywords: Humans; Models, Molecular; Protein Conformation; Molecular Sequence Data; Crystallography, X-Ray; Binding Sites; HIV-1/*enzymology; X-Ray Diffraction; Drug Design; HIV Protease Inhibitors/chemistry/*pharmacology; HIV Protease/chemical synthesis/chemistry/*metabolism; Oligopeptides/chemistry/*pharmacology

Insights into the structure/function of hepatocyte growth factor/scatter factor from studies with individual domains - Holmes, O.; Pillozzi, S.; Deakin, J. A.; Carafoli, F.; Kemp, L.; Butler, P. J.; Lyon, M.; Gherardi, E. (J. Mol. Biol., 2007)
Hepatocyte growth factor/scatter factor (HGF/SF), the ligand for the receptor tyrosine kinase encoded by the c-Met proto-oncogene, is a multidomain protein structurally related to the pro-enzyme plasminogen and with major roles in development, tissue regeneration and cancer. We have expressed the N-terminal (N) domain, the four kringle domains (K1 to K4) and the serine proteinase homology domain (SP) of HGF/SF individually in yeast or mammalian cells and studied their ability to: (i) bind the Met receptor as well as heparan sulphate and dermatan sulphate co-receptors, (ii) activate Met in target cells and, (iii) map their binding sites onto the beta-propeller domain of Met. The N, K1 and SP domains bound Met directly with comparable affinities (K(d)=2.4, 3.3 and 1.4 microM). The same domains also bound heparin with decreasing affinities (N>K1>>SP) but only the N domain bound dermatan sulphate. Three kringle domains (K1, K2 and K4) displayed agonistic activity on target cells. In contrast, the N and SP domains, although capable of Met binding, displayed no or little activity. Further, cross-linking experiments demonstrated that both the N domain and kringles 1-2 bind the beta-chain moiety (amino acid residues 308-514) of the Met beta-propeller. In summary, the K1, K2 and K4 domains of HGF/SF are sufficient for Met activation, whereas the N and SP domains are not, although the latter domains contribute additional binding sites necessary for receptor activation by full length HGF/SF. The results provide new insights into the structure/function of HGF/SF and a basis for engineering the N and K1 domains as receptor antagonists for cancer therapy.
0022-2836 (Print) 0022-2836 (Linking) Journal Article Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: MRC Centre, Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK. number: 2 accession-num: 17258232
Keywords: Animals; Humans; Mutation; Cell Line; Protein Binding; Phosphorylation; Mice; Protein Structure, Tertiary; Structure-Activity Relationship; Binding Sites; Dogs; Cell Movement; Cricetinae; Cricetulus; Dermatan Sulfate/*metabolism; Electrophoretic Mobility Shift Assay; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases/metabolism; Heparitin Sulfate/*metabolism; Hepatocyte Growth Factor/genetics/metabolism/*physiology; Kringles; Pichia; Proto-Oncogene Proteins c-met/*metabolism; Serine Endopeptidases/genetics

Corrigendum to "N-Alkyl cysteine-assisted thioesterification of peptides": [Tetrahedron Lett. 48 (2007) 25] - Hojo, Hironobu; Onuma, Yuko; Akimoto, Yuri; Nakahara, Yuko; Nakahara, Yoshiaki (Tetrahedron Lett., 2007)
0040-4039
The following values have no corresponding Zotero field: number: 7

N-Alkyl cysteine-assisted thioesterification of peptides - Hojo, H.; Onuma, Y.; Akimoto, Y.; Nakahara, Y.; Nakahara, Y. (Tetrahedron Lett., 2007)
Keywords: #nosource

Site-specific protein and peptide immobilization on a biosensor surface by pulsed native chemical ligation - Helms, Brett; van Baal, Ingrid; Merkx, Maarten; Meijer, E. W. (ChemBioChem, 2007)
The following values have no corresponding Zotero field: number: 15 publisher: WILEY-VCH Verlag
Keywords: native chemical ligation; biosensors; protein immobilization; surface plasmon resonance

Thermodynamic analysis of beta-sheet secondary structure by backbone thioester exchange - Hadley, E. B.; Witek, A. M.; Freire, F.; Peoples, A. J.; Gellman, S. H. (Angew. Chem. Int. Ed., 2007)
Hadley, Erik B Witek, Alex M Freire, Felix Peoples, Aaron J Gellman, Samuel H GM-61238/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Germany Angewandte Chemie (International ed. in English) Angew Chem Int Ed Engl. 2007;46(37):7056-9.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53726, USA. number: 37 edition: 2007/08/11 accession-num: 17691093
Keywords: Amino Acid Sequence; Molecular Structure; Molecular Sequence Data; Sequence Alignment; Nuclear Magnetic Resonance, Biomolecular; *Protein Structure, Secondary; *Thermodynamics; Proteins/*chemistry/genetics

Concepts in sumoylation: a decade on - Geiss-Friedlander, R.; Melchior, F. (Nat. Rev. Mol. Cell. Biol., 2007)
A decade has passed since SUMO (small ubiquitin-related modifier) was discovered to be a reversible post-translational protein modifier. During this time many enzymes that participate in regulated SUMO-conjugation and -deconjugation pathways have been identified and characterized. In parallel, the search for SUMO substrates has produced a long list of targets, which appear to be involved in most cellular functions. Sumoylation is a highly dynamic process and its outcomes are extremely diverse, ranging from changes in localization to altered activity and, in some cases, stability of the modified protein. At first glance, these effects have nothing in common; however, it seems that they all result from changes in the molecular interactions of the sumoylated proteins.
Geiss-Friedlander, Ruth Melchior, Frauke Research Support, Non-U.S. Gov't Review England Nature reviews. Molecular cell biology Nat Rev Mol Cell Biol. 2007 Dec;8(12):947-56.
The following values have no corresponding Zotero field: auth-address: Department of Biochemie I, Faculty of Medicine, University of Goettingen, Humboldt Allee 23, 37073 Goettingen, Germany. number: 12 edition: 2007/11/15 accession-num: 18000527
Keywords: Animals; Humans; Small Ubiquitin-Related Modifier Proteins/*metabolism; *Protein Processing, Post-Translational; Proteins/metabolism

Second-generation sugar-assisted ligation: a method for the synthesis of cysteine-containing glycopeptides - Ficht, S.; Payne, R. J.; Brik, A.; Wong, C. H. (Angew. Chem. Int. Ed., 2007)
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Germany
The following values have no corresponding Zotero field: auth-address: The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. alt-title: Angewandte Chemie (International ed number: 31 accession-num: 17607677
Keywords: Amino Acid Sequence; Molecular Sequence Data; Glycosylation; Cysteine/analysis/*chemistry; Glycopeptides/*chemical synthesis/chemistry; Carbohydrates/*chemistry

Convergent chemical synthesis and high-resolution x-ray structure of human lysozyme - Durek, T.; Torbeev, V. Y.; Kent, S. B. H. (Proc. Natl. Acad. Sci. U. S. A., 2007)
In this article, we report the total chemical synthesis of human lysozyme. Lysozyme serves as a widespread model system in various fields of biochemical research, including protein folding, enzyme catalysis, and amyloidogenesis. The 130-aa wild-type polypeptide chain of the human enzyme was assembled from four polypeptide segments by using native chemical ligation in a fully convergent fashion. Key to the assembly strategy is the application of the recently developed kinetically controlled ligation methodology, which provides efficient control over the ligation of two peptide (alpha)thioesters to yield a unique product. This result enables the facile preparation of a 64-residue peptide (alpha)thioester; this segment is joined by native chemical ligation to a 66-aa Cys peptide, to yield the target 130-aa polypeptide chain. The synthetic polypeptide chain was folded in vitro into a defined tertiary structure with concomitant formation of four disulfides, as shown by 2D TOCSY NMR spectroscopy. The structure of the synthetic human lysozyme was confirmed by high-resolution x-ray diffraction, giving the highest-resolution structure (1.04 A) observed to date for this enzyme. Synthetic lysozyme was obtained in good yield and excellent purity and had full enzymatic activity. This facile and efficient convergent synthesis scheme will enable preparation of unique chemical analogs of the lysozyme molecule and will prove useful in numerous areas of lysozyme research in the future.
0027-8424 (Print) 0027-8424 (Linking) Journal Article Research Support, U.S. Gov't, Non-P.H.S.
The following values have no corresponding Zotero field: auth-address: Institute for Biophysical Dynamics, Department of Biochemistry and Molecular Biology, University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA. number: 12 accession-num: 17360367
Keywords: Amino Acid Sequence; Humans; Models, Molecular; Kinetics; Molecular Sequence Data; Chromatography, High Pressure Liquid; Peptides/chemical synthesis/chemistry; Protein Folding; Crystallography, X-Ray; Protein Structure, Secondary; Disulfides/metabolism; Muramidase/*chemical synthesis/*chemistry/metabolism

Amino Acid and Peptide Synthesis and Functionalization by the Reaction of Thioacids with 2,4-Dinitrobenzenesulfonamides - Crich, David; Sana, Kasinath; Guo, Songpo (Organic Letters, 2013)
doi: 10.1021/ol701583t
The following values have no corresponding Zotero field: number: 22 publisher: American Chemical Society

Native chemical ligation at phenylalanine - Crich, D.; Banerjee, A. (J. Am. Chem. Soc., 2007)
0002-7863 (Print) 0002-7863 (Linking) Journal Article Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607-7061, USA. dcrich@chem.wayne.edu number: 33 accession-num: 17658806
Keywords: Cysteine/chemistry; Peptides/*chemical synthesis; Sulfhydryl Compounds/chemical synthesis/*chemistry; Phenylalanine/*analogs & derivatives/*chemistry

Solid-phase peptide synthesis: from standard procedures to the synthesis of difficult sequences - Coin, I.; Beyermann, M.; Bienert, M. (Nat. Protocols, 2007)
10.1038/nprot.2007.454
The following values have no corresponding Zotero field: number: 12 publisher: Nature Publishing Group

Development of efficient methods for accomplishing cysteine-free peptide and glycopeptide coupling - Chen, G.; Wan, Q.; Tan, Z.; Kan, C.; Hua, Z.; Ranganathan, K.; Danishefsky, S. J. (Angew. Chem. Int. Ed., 2007)
Chen, Gong Wan, Qian Tan, Zhongping Kan, Cindy Hua, Zihao Ranganathan, Krishnakumar Danishefsky, Samuel J CA28824/CA/NCI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Germany Angewandte Chemie (International ed. in English) Angew Chem Int Ed Engl. 2007;46(39):7383-7.
The following values have no corresponding Zotero field: auth-address: Laboratory of Bioorganic Chemistry, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 106, New York, NY 10021, USA. number: 39 edition: 2007/09/11 accession-num: 17828726
Keywords: Esters/chemistry; Molecular Structure; Peptides/*chemical synthesis/chemistry; Cysteine/*chemistry; Molecular Sequence Data; Glycosylation; Phenols/chemistry

Auxiliary-mediated site-specific peptide ubiquitylation - Chatterjee, C.; McGinty, R. K.; Pellois, J. P.; Muir, T. W. (Angew. Chem. Int. Ed., 2007)
Chatterjee, Champak McGinty, Robert K Pellois, Jean-Philippe Muir, Tom W GM 07739/GM/NIGMS NIH HHS/United States Research Support, N.I.H., Extramural Germany Angewandte Chemie (International ed. in English) Angew Chem Int Ed Engl. 2007;46(16):2814-8.
The following values have no corresponding Zotero field: auth-address: The Laboratory of Synthetic Protein Chemistry, The Rockefeller University, Box 223, 1230 York Avenue, New York, NY 10021, USA. number: 16 edition: 2007/03/17 accession-num: 17366504
Keywords: Peptides/*chemical synthesis/*chemistry; Ligands; Photolysis; Indicators and Reagents; Resins, Synthetic/chemistry; Ubiquinone/*chemistry

Sugar-assisted ligation for the synthesis of glycopeptides - Brik, A.; Wong, C. H. (Chemistry, 2007)
Chemical synthesis of glycoproteins from readily available materials is a powerful method for obtaining a pure product with full control of its atomic structure. Sugar-assisted ligation (SAL) is an emerging approach that allows the synthesis of a large glycopeptide from two unprotected fragments. Contrary to other ligation methods that are limited to the use of a cysteine residue or depend on external auxiliary, SAL takes advantage of the existing sugars in glycopeptides to promote proximity between the two peptides to facilitate an amide bond formation.
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review Germany
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Ben Gurion University, Beer Sheva, Israel. abrik@bgu.ac.il alt-title: Chemistry (Weinheim an der Bergstrasse, Germany) number: 20 accession-num: 17508364
Keywords: Molecular Structure; Molecular Sequence Data; Carbohydrate Sequence; Glycopeptides/*chemical synthesis/chemistry; Carbohydrates/*chemistry

Staudinger ligation of peptides at non-glycyl residues - Soellner, M. B.; Tam, A.; Raines, R. T. (J. Org. Chem., 2006)
The Staudinger ligation provides a means to form an amide bond between a phosphinothioester and azide. This reaction holds promise for the ligation of peptides en route to the total chemical synthesis of proteins. (Diphenylphosphino)methanethiol is the most efficacious of known reagents for mediating the Staudinger ligation of peptides, providing high (> 90%) isolated yields for equimolar couplings in which a glycine residue is at the nascent junction. Surprisingly, the yields are lower (< 50%) for non-glycyl couplings due to an aza-Wittig reaction that diverts the reaction toward a phosphonamide byproduct. Here, the partitioning of the reaction toward Staudinger ligation (and away from the aza-Wittig reaction) is shown to increase with increasing electron density on phosphorus. This electron density can be tuned either by installing functional groups on the phenyl substituents of (diphenylphosphino)methanethiol or by changing the polarity of the solvent. Installing p-methoxy groups and using a solvent of low polarity (such as toluene or dioxane) provide especially high (> 80%) isolated yields for the ligation of two non-glycyl residues. These conditions retain the high chemoselectivity of the reaction and do not lead to a substantial change in reaction rate. The traceless Staudinger ligation is now poised to enable the iterative ligation of peptides with little regard for their sequence, as well as the synthesis of amide bonds for other purposes.
0022-3263 (Print) 0022-3263 (Linking) Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA. number: 26 accession-num: 17168602
Keywords: Stereoisomerism; Esters/chemistry; Molecular Structure; Peptides/*chemical synthesis/chemistry; Azides/chemistry; Magnetic Resonance Spectroscopy; Water/chemistry; Ligands; Sensitivity and Specificity; Amides/chemical synthesis/chemistry; Dioxanes/chemistry; Furans/chemistry

Reaction mechanism and kinetics of the traceless Staudinger ligation - Soellner, M. B.; Nilsson, B. L.; Raines, R. T. (J. Am. Chem. Soc., 2006)
The traceless Staudinger ligation enables the formation of an amide bond between a phosphinothioester (or phosphinoester) and an azide without the incorporation of residual atoms. Here, the coupling of peptides by this reaction was characterized in detail. Experiments with [(18)O]H(2)O indicated that the reaction mediated by (diphenylphosphino)methanethiol proceeded by S-->N acyl transfer of the iminophosphorane intermediate to form an amidophosphonium salt, rather than by an aza-Wittig reaction and subsequent hydrolysis of the resulting thioimidate. A continuous (13)C NMR-based assay revealed that the rate-determining step in the Staudinger ligation of glycyl residues mediated by (diphenylphosphino)methanethiol was the formation of the initial phosphazide intermediate. Less efficacious coupling reagents and reaction conditions led to the accumulation of an amine byproduct (which resulted from a Staudinger reduction) or phosphonamide byproduct (which resulted from an aza-Wittig reaction). The Staudinger ligation mediated by (diphenylphosphino)methanethiol proceeded with a second-order rate constant (7.7 x 10(-3) M(-1) s(-1)) and yield (95%) that was unchanged by the addition of exogenous nucleophiles. Ligations mediated by phosphinoalcohols had lower rate constants or less chemoselectivity. Accordingly, (diphenylphosphino)methanethiol was judged to be the most efficacious known reagent for effecting the traceless Staudinger ligation.
0002-7863 (Print) 0002-7863 (Linking) Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA. number: 27 accession-num: 16819875
Keywords: Stereoisomerism; Kinetics; Molecular Structure; Peptides/chemistry; Time Factors; Ligands; Azides/*chemistry; Sensitivity and Specificity; Magnetic Resonance Spectroscopy/methods; Organothiophosphorus Compounds/*chemistry

The chemical synthesis of the GstI protein by NCL on a X-Met site - Saporito, A.; Marasco, D.; Chambery, A.; Botti, P.; Monti, S. M.; Pedone, C.; Ruvo, M. (Biopolymers, 2006)
The small GstI protein (63 amino acids) of Rhizobium leguminosarum is the endogenous inhibitor of the glnII (glutamine synthetase II) gene expression. It has been suggested that GstI has a predominantly beta-structure and mediates the block of translation and stabilization of glnII mRNA through direct binding to its 5' untranslated region. Because of the unavailability of adequate amounts of purified recombinant protein, the mechanism as well as the protein tridimensional structure remain very poorly understood. To obtain the full-length protein, we have undertaken the chemical synthesis of the protein by different approaches. In a first attempt, the stepwise synthesis was unsuccessful, with strong aggregation experienced on the N-terminal side, after residue 44 from the C-terminus. In a second approach, we set up the conditions to carry out a native chemical ligation (NCL). Albeit the protein contains two Cysteine residues, located at positions 40 and 47, to minimize the size of the N-terminal segment to be synthesized, we have devised an alternative strategy of ligation on Met32, utilizing homoCys as the ligating moiety and then alkylating the resulting polypeptide with methyl iodide. New conditions to quantitatively methylate thiol groups in complex polypeptides have been conceived, obtaining the protein in very good yields and purity. A CD spectroscopy investigation has revealed that the protein does not adopt canonical secondary structures but is very rich in beta-structure (approximately 60%), in agreement with a previous study carried out on samples obtained by recombinant methods.
Journal Article Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: Istituto di Biostrutture e Bioimmagini del CNR, Sezione Biostrutture, NAPOLI, via Mezzocannone 16, 80134 Napoli, Italy. alt-title: Biopolymers number: 5 accession-num: 16888773
Keywords: Amino Acid Sequence; Cysteine/chemistry; Chromatography, High Pressure Liquid; Mass Spectrometry; Circular Dichroism; Methionine/*chemistry; Bacterial Proteins/*chemical synthesis/chemistry; Protein Structure, Secondary; Homocysteine/metabolism; Repressor Proteins/*chemical synthesis/chemistry

A study of cysteamine ionization in solution by Raman spectroscopy and theoretical modeling - Riauba, Laurynas; Niaura, Gediminas; Eicher-Lorka, Olegas; Butkus, Eugenijus (J. Phys. Chem. A, 2006)
doi: 10.1021/jp063816g 1089-5639 doi: 10.1021/jp063816g
The following values have no corresponding Zotero field: number: 50 publisher: American Chemical Society

Impact of bronchial epithelium on dendritic cell migration and function: modulation by the bacterial motif KpOmpA - Pichavant, M.; Taront, S.; Jeannin, P.; Breuilh, L.; Charbonnier, A. S.; Spriet, C.; Fourneau, C.; Corvaia, N.; Heliot, L.; Brichet, A.; Tonnel, A. B.; Delneste, Y.; et al. (J. Immunol., 2006)
Mucosal immune response depends on the surveillance network established by dendritic cells (DC), APC localized within the epithelium. Bronchial epithelial cells (BEC) play a pivotal role both in the host defense and in the pathogenesis of inflammatory airway disorders. We previously showed that the outer membrane protein A from Klebsiella pneumoniae (KpOmpA), a pathogen-associated molecular pattern (PAMP) derived from Klebsiella pneumoniae, activates BEC. In this study, we evaluated the consequences of this activation on DC traffic and functions. KpOmpA significantly increased the production of CCL2, CCL5, CXCL10, and CCL20 by BEC. Stimulation of BEC increased their chemotactic activity for monocyte-derived DC (MDDC) precursors, through CCL5 and CXCL10 secretion. BEC/MDDC precursor coculture leads to an ICAM-1-dependent accelerated differentiation and enhanced maturation of MDDC. BEC/DC interactions did not affect the capacity of DC to induce T cell proliferation. However, DC preincubated with BEC increased significantly the IL-10 production by autologous T cells. Basolateral and intraepithelial DC differently enhance IL-4 and/or IL-10 synthesis according to the condition of stimulation. In vivo, intranasal injections of KpOmpA into BALB/c mice induced the recruitment of CD11c(+) and I-A(d+) myeloid DC associated with bronchial epithelium activation as evidenced by CCL20 expression. These data show that KpOmpA-exposed BEC participate in the homeostasis of myeloid DC network, and regulate the induction of local immune response.
Pichavant, Muriel Taront, Solenne Jeannin, Pascale Breuilh, Laetitia Charbonnier, Anne-Sophie Spriet, Corentin Fourneau, Catherine Corvaia, Nathalie Heliot, Laurent Brichet, Anne Tonnel, Andre-Bernard Delneste, Yves Gosset, Philippe Baltimore, Md. : 1950 J Immunol. 2006 Nov 1;177(9):5912-9.
The following values have no corresponding Zotero field: auth-address: Institut National de la Sante et de la Recherche Medicale (INSERM) U774, Institut Pasteur de Lille, 1 rue de Professeur Calmette, BP 245, 59019 Lille cedex, France. number: 9 edition: 2006/10/24 accession-num: 17056515 work-type: Research Support, Non-U.S. Gov't
Keywords: Animals; Humans; Mice; Cell Movement; Administration, Intranasal; Bacterial Outer Membrane Proteins/administration & dosage/*immunology; Bronchi/cytology/drug effects/*immunology; CD11c Antigen/analysis; Chemokines/metabolism; Coculture Techniques; Cytokines/metabolism; Dendritic Cells/*immunology; Epithelium/drug effects/immunology; Histocompatibility Antigens Class II/analysis; Intercellular Adhesion Molecule-1/metabolism; Mice, Inbred BALB C; Myeloid Cells/immunology; T-Lymphocytes/immunology

Semisynthetic proteins in mechanistic studies: using chemistry to go where nature can't - Pellois, J. P.; Muir, T. W. (Curr. Opin. Chem. Biol., 2006)
The manipulation of the chemical structure of proteins beyond what is feasible with standard genetics, offers a powerful strategy to investigate protein mechanisms. By allowing the incorporation of biophysical probes, unnatural amino acids, and post-translational modifications in proteins, chemistry-driven approaches have greatly contributed to the understanding of the molecular basis of protein function.
1367-5931 (Print) 1367-5931 (Linking) Journal Article Research Support, N.I.H., Extramural Review
The following values have no corresponding Zotero field: auth-address: The Laboratory of Synthetic Protein Chemistry, The Rockefeller University, New York, NY 10021, USA. number: 5 accession-num: 16935551
Keywords: Animals; Amino Acids/chemistry; Structure-Activity Relationship; Protein Processing, Post-Translational; Protein Engineering/methods; GTP Phosphohydrolases/chemistry; Histones/chemistry; Ion Channels; Molecular Probes; Protein Tyrosine Phosphatases/chemistry; Proteins/*chemical synthesis/*chemistry/physiology; Ribonucleotide Reductases/chemistry

Cysteine-derived S-protected oxazolidinones: Potential chemical devices for the preparation of peptide thioesters - Ohta, Yusuke; Itoh, Saori; Shigenaga, Akira; Shintaku, Saori; Fujii, Nobutaka; Otaka, Akira (Org. Lett., 2006)
null
doi: 10.1021/ol052755m 1523-7060 doi: 10.1021/ol052755m
The following values have no corresponding Zotero field: number: 3 publisher: American Chemical Society

Catalysis of electron transfer by selenocysteine - Nauser, T.; Dockheer, S.; Kissner, R.; Koppenol, W. H. (Biochemistry, 2006)
Selenium is an essential element that is involved in biological redox processes. The electrode potentials of the selenocysteine half-reactions RSe(*) + e(-) --> RSe-, (RSeSeR)(*)(-) + e(-) --> 2 RSe(-), and RSeSeR + 2 e(-) --> 2 RSe(-) [E degrees' (pH 7)] are +0.43, +0.18, and -0.38 V, respectively, at pH 7. The spectra of RSe(*) and (RSeSeR)(*)(-) are characterized by absorption maxima at 460 nm (epsilon = 560 M(-)(1) cm(-)(1)) and 455 nm (epsilon = 7100 M(-)(1) cm(-)(1)), respectively. The bond dissociation energy of RSe-H has been calculated, and the value of 310 kJ/mol is in agreement with literature values. In comparison with the sulfur analogue cysteine, the more facile accessibility of the radical oxidation state is striking and may have biological implications, such as in mediation of one-electron- and two-electron-transfer processes, as illustrated by catalysis by selenocysteine of the electron transfer between dithiothreitol and benzyl viologen.
Journal Article Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: Laboratorium fur Anorganische Chemie, ETH Honggerberg, CH-8093 Zurich, Switzerland. alt-title: Biochemistry number: 19 accession-num: 16681376
Keywords: Hydrogen-Ion Concentration; Catalysis; Selenocysteine/*chemistry; Spectrophotometry, Ultraviolet; Electrochemistry; Electron Transport; Lasers

Efficient microwave-assisted tandem N- to S-acyl transfer and thioester exchange for the preparation of a glycosylated peptide thioester - Nagaike, Fumihiro; Onuma, Yuko; Kanazawa, Chie; Hojo, Hironobu; Ueki, Akiharu; Nakahara, Yuko; Nakahara, Yoshiaki (Org. Lett., 2006)
null
doi: 10.1021/ol0616034 1523-7060 doi: 10.1021/ol0616034
The following values have no corresponding Zotero field: number: 20 publisher: American Chemical Society

Synthetic seleno-glutaredoxin 3 analogues are highly reducing oxidoreductases with enhanced catalytic efficiency - Metanis, N.; Keinan, E.; Dawson, P. E. (J. Am. Chem. Soc., 2006)
Selenoenzymes have a central role in maintaining cellular redox potential. These enzymes have selenenylsulfide bonds in their active sites that catalyze the reduction of peroxides, sulfoxides, and disulfides. The selenol/disufide exchange reaction is common to all of these enzymes, and the active site redox potential reflects the ratio between the forward and reverse rates of this reaction. The preparation of enzymes containing selenocysteine (Sec) is experimentally challenging. As a result, little is known about the kinetic role of selenols in enzyme active sites, and the redox potential of a selenenylsulfide or diselenide bond in a protein has not been experimentally determined. To fully evaluate the effects of Sec on oxidoreductase redox potential and kinetics, glutaredoxin 3 (Grx3) and all three Sec variants of its conserved (11)CXX(14)C active site were chemically synthesized. Grx3, Grx3(C11U), and Grx3(C14U) exhibited redox potentials of -194, -260, and -275 mV, respectively. The position of redox equilibrium between Grx3(C11U-C14U) (-309 mV) and thioredoxin (Trx) (-270 mV) suggests a possible role for diselenide bonds in biological systems. Kinetic analysis is consistent with the hypothesis that the lower redox potentials of the Sec variants result primarily from the greater nucleophilicity of the active site selenium rather than its role as either a leaving group or a "central atom" in the exchange reaction. The 10(2)-10(4)-fold increase in the rate of Trx reduction by the seleno-Grx3 analogues demonstrates that oxidoreductases containing either selenenyl-sulfide or diselenide bonds can have physiologically compatible redox potentials and enhanced reduction kinetics in comparison with their sulfide counterparts.
GM 059380/GM/NIGMS NIH HHS/United States R01 GM059380/GM/NIGMS NIH HHS/United States R01 GM059380-08/GM/NIGMS NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. United States
The following values have no corresponding Zotero field: auth-address: Department of Chemistry and Institute of Catalysis Science and Technology, Technion-Israel Institute of Technology, Technion City, Haifa 32000, Israel. alt-title: Journal of the American Chemical Society number: 51 accession-num: 17177418
Keywords: Protein Conformation; Molecular Structure; Catalysis; Oxidation-Reduction; Thermodynamics; Time Factors; Structure-Activity Relationship; Binding Sites; Protein Structure, Secondary; Glutaredoxins; Organoselenium Compounds/*chemical synthesis/*chemistry; Oxidoreductases/*chemistry

Residue-level NMR view of the urea-driven equilibrium folding transition of SUMO-1 (1-97): native preferences do not increase monotonously - Kumar, A.; Srivastava, S.; Kumar Mishra, R.; Mittal, R.; Hosur, R. V. (J. Mol. Biol., 2006)
SUMO-1 (1-97) is a crucial protein in the machinery of post-translational modifications. We observed by circular dichroism and fluorescence spectroscopy that urea-induced unfolding of this protein is a complex process with the possibility of occurrence of detectable intermediates along the way. The tertiary structure is completely lost around approximately 4.5 M urea with a transition mid-point at 2.53 M urea, while the secondary structure unfolding seems to show two transitions, with mid-points at 2.42 M and 5.69 M urea. We have elucidated by systematic urea titration, the equilibrium residue level structural and dynamics changes along the entire folding/unfolding transition by multidimensional NMR. With urea dilution, the protein is seen to progressively lose most of the broad beta-domain structural preferences present at 8 M urea, acquire some helical propensities at 5 M urea, and lose some of them again on further dilution of urea. Between 3 M and 2 M urea, the protein starts afresh to acquire native structural features. These observations are contrary to the conventional notion that proteins fold with monotonously increasing native-type preferences. For folding below approximately 3 M urea, the region around the alpha1 helix appears to be a potential folding initiation site. The folding seems to start with a collapse into native-like topologies, at least in parts, and is followed by formation of secondary and tertiary structure, perhaps by cooperative rearrangements. The motional characteristics of the protein show sequence-dependent variation as the concentration of urea is progressively reduced. At the sub-nanosecond level, the features are extremely unusual for denatured states, and only certain segments corresponding to the flexible regions in the native protein display these motions at the different concentrations of urea.
Kumar, Ashutosh Srivastava, Sudha Kumar Mishra, Ram Mittal, Rohit Hosur, Ramakrishna V Research Support, Non-U.S. Gov't England Journal of molecular biology J Mol Biol. 2006 Aug 4;361(1):180-94. Epub 2006 Jun 19.
The following values have no corresponding Zotero field: auth-address: Department of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai, India. number: 1 edition: 2006/07/11 accession-num: 16824543
Keywords: Humans; *Protein Folding; Amino Acids/chemistry/*metabolism; Nuclear Magnetic Resonance, Biomolecular; Protein Denaturation; *Urea; Peptide Fragments/chemistry/metabolism; SUMO-1 Protein/*chemistry/*metabolism

Insights into the mechanism and catalysis of the native chemical ligation reaction - Johnson, E. C.; Kent, S. B. H. (J. Am. Chem. Soc., 2006)
Native chemical ligation of unprotected peptide segments involves reaction between a peptide-alpha-thioester and a cysteine-peptide, to yield a product with a native amide bond at the ligation site. Peptide-alpha-thioalkyl esters are commonly used because of their ease of preparation. These thioalkyl esters are rather unreactive so the ligation reaction is catalyzed by in situ transthioesterification with thiol additives. The most common thiol catalysts used to date have been either a mixture of thiophenol/benzyl mercaptan, or the alkanethiol MESNA. Despite the use of these thiol catalysts, ligation reactions typically take 24-48 h. To gain insight into the mechanism of native chemical ligaton and in order to find a better catalyst, we investigated the use of a number of thiol compounds. Substituted thiophenols with pK(a) > 6 were found to best combine the ability to exchange rapidly and completely with thioalkyl esters, and to then act as effective leaving groups in reaction of the peptide-thioester with the thiol side chain of a cysteine-peptide. A highly effective and practical catalyst was (4-carboxylmethyl)thiophenol ('MPAA'), a nonmalodorous, water-soluble thiol. Use of MPAA gave an order of magnitude faster reaction in model studies of native chemical ligation and in the synthesis of a small protein, turkey ovomucoid third domain (OMTKY3). MPAA should find broad use in native chemical ligation and in the total synthesis of proteins.
0002-7863 (Print) 0002-7863 (Linking) Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.
The following values have no corresponding Zotero field: auth-address: Department of Biochemistry and Molecular Biology, The University of Chicago, Illinois 60637, USA. number: 20 accession-num: 16704265
Keywords: Hydrogen-Ion Concentration; Cysteine/chemistry; Esters/chemistry; Catalysis; Proteins/*chemical synthesis; Peptides/chemical synthesis/chemistry; Sulfhydryl Compounds/chemistry; Ovomucin/chemical synthesis; Phenylacetates/chemistry

Total chemical synthesis, folding, and assay of a small protein on a water-compatible solid support - Johnson, E. C.; Durek, T.; Kent, S. B. H. (Angew. Chem. Int. Ed., 2006)
1433-7851 (Print) 1433-7851 (Linking) Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.
The following values have no corresponding Zotero field: auth-address: Institute for Biophysical Dynamics, Department of Biochemistry, University of Chicago, IL 60637, USA. number: 20 accession-num: 16596681
Keywords: Peptides/*chemistry; Proteins/*chemical synthesis; *Protein Folding; Time Factors; Models, Chemical; *Biological Assay; Water/*chemistry; Laboratory Techniques and Procedures; Plant Proteins/chemistry; Resins, Synthetic/*chemistry; Trypsin Inhibitors/chemistry

Energetics of an n->p* interaction that impacts protein structure - Hodges, J. A.; Raines, R. T. (Org. Lett., 2006)
[structure: see text] The trans/cis ratio of the amide bond in N-formylproline phenylesters correlates with electron withdrawal by a para substituent. The slope of the Hammett plot (rho = 0.26) is indicative of a substantial effect. This effect arises from a favorable n --> pi interaction between the amide oxygen and ester carbonyl. In a polypeptide chain, an analogous interaction can stabilize the conformation of trans peptide bonds, alpha-helices, and polyproline type-II helices.
AR48057/AR/NIAMS NIH HHS/United States F32 AR048057/AR/NIAMS NIH HHS/United States R01 AR044276-11/AR/NIAMS NIH HHS/United States AR44276/AR/NIAMS NIH HHS/United States R01 AR044276/AR/NIAMS NIH HHS/United States F32 AR048057-03/AR/NIAMS NIH HHS/United States Journal Article Research Support, N.I.H., Extramural United States
The following values have no corresponding Zotero field: auth-address: Departments of Chemistry and Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA. alt-title: Organic letters number: 21 accession-num: 17020280
Keywords: Protein Conformation; Stereoisomerism; Proteins/*chemistry; Thermodynamics; *Models, Chemical

The reduction of oxidized methionine residues in peptide thioesters with NH4I-Me2S - Hackenberger, Christian P. R. (Org. Biomol. Chem., 2006)
Oxidized methionine residues in peptide thioesters can be reduced rapidly with NH4I to the corresponding sulfide by using Me2S as coreductant. Comparative reduction studies employing a 28-amino acid peptide thioester with an N-terminal methionine oxide as model system revealed the importance of the Me2S addition to avoid hydrolysis of the reactive thioester functionality. In addition, an NH4I-Me2S containing cleavage cocktail has been used for the global deprotection of various thioesters which revealed no hydrolysis or oxidative side products. These results demonstrate the general applicability of sulfoxides as protecting groups in advanced peptide synthesis techniques by facilitating the preparation and handling of methionine containing peptide thioesters for native chemical ligation (NCL).
1477-0520 10.1039/B603543D
The following values have no corresponding Zotero field: number: 11 publisher: The Royal Society of Chemistry

DNA-catalyzed transfer of a reporter group - Grossmann, T. N.; Seitz, O. (J. Am. Chem. Soc., 2006)
Herein we describe a novel DNA-catalyzed transfer of a reporter group from a donating to an accepting oligo-peptide nucleic acid (PNA), generating high catalytic turnover numbers in a DNA-sequence specific manner. The demonstrated transfer of the Dabcyl group was designed to switch on emission of a fluorescein dye while switching off emission of a rhodamine dye. This setup allows the highly sensitive and selective detection of DNA-sequences in real time.
Grossmann, Tom N Seitz, Oliver J Am Chem Soc. 2006 Dec 13;128(49):15596-7.
The following values have no corresponding Zotero field: auth-address: Institut fur Chemie, Humboldt-Universitat zu Berlin, Brook-Taylor-Strasse 2, D-12489 Berlin, Germany. alt-title: Journal of the American Chemical Society number: 49 edition: 2006/12/07 accession-num: 17147362 work-type: Research Support, Non-U.S. Gov't
Keywords: Catalysis; Base Sequence; Fluorescent Dyes/chemistry; Rhodamines/*chemistry; *Biosensing Techniques; Biological Transport, Active/physiology; DNA/chemistry/*metabolism; Fluoresceins/*chemistry; Genes, Reporter; Nucleic Acid Hybridization; Templates, Genetic

ortho- and meta-substituted aromatic thiols are efficient redox buffers that increase the folding rate of a disulfide-containing protein - Gough, J. D.; Barrett, E. J.; Silva, Y.; Lees, W. J. (J. Biotechnol., 2006)
Thiol based redox buffers are used to enhance the folding rates of disulfide-containing proteins in vitro. Traditionally, small molecule aliphatic thiols such as glutathione are employed. Recently, we have demonstrated that aromatic thiols can further enhance protein-folding rates. In the presence of para-substituted aromatic thiols the folding rate of a disulfide-containing protein was increased by 4-23 times over that measured for glutathione. However, several important practical issues remain to be addressed. Aromatic thiols have never been tested in the presence of denaturants such as guanidine hydrochloride. Only two of the para-substituted aromatic thiols previously examined are commercially available. To expand the number of aromatic thiols for protein folding, several commercially available meta- and ortho-substituted aromatic thiols were studied. Furthermore, an ortho-substituted aromatic thiol, easily obtained from inexpensive starting materials, was investigated. Folding rates of scrambled ribonuclease A at pH 6.0, 7.0 and 7.7, with ortho- and meta-substituted aromatic thiols, were up to 10 times greater than those with glutathione. In the presence of the common denaturant guanidine hydrochloride (0.5M) aromatic thiols provided 100% yield of active protein while maintaining equivalent folding rates.
T34 GM08771/GM/NIGMS NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Netherlands
The following values have no corresponding Zotero field: auth-address: Department of Chemistry and Biochemistry, Florida International University, Miami, FL 33199, USA. alt-title: Journal of biotechnology number: 1 accession-num: 16616966
Keywords: Kinetics; Hydrogen-Ion Concentration; Dose-Response Relationship, Drug; Molecular Structure; Proteins/*chemistry; *Protein Folding; Oxidation-Reduction; Disulfides/*chemistry; Buffers; Glutathione/chemistry/pharmacology; Guanidine/chemistry/pharmacology; Protein Conformation/drug effects; Ribonuclease, Pancreatic/chemistry/metabolism; Sulfhydryl Compounds/*chemistry/pharmacology

Density functional theory study of the thiolysis reaction in penicillins - Garcías, R. C.; Coll, M.; Donoso, J.; Muñoz, F. (J. Mol. Struct: THEOCHEM, 2006)
0166-1280 doi: DOI: 10.1016/j.theochem.2006.07.001
The following values have no corresponding Zotero field: number: 1-3
Keywords: [beta]-Lactam antibiotics; Theoretical calculations; Thiolysis of penicillins

ChemMatrix, a poly(ethylene glycol)-based support for the solid-phase synthesis of complex peptides - Garcia-Martin, F.; Quintanar-Audelo, M.; Garcia-Ramos, Y.; Cruz, L. J.; Gravel, C.; Furic, R.; Cote, S.; Tulla-Puche, J.; Albericio, F. (J. Comb. Chem., 2006)
CM (ChemMatrix) resin is a new, totally poly(ethylene glycol) (PEG)-based resin, made exclusively from primary ether bonds and, therefore, highly chemically stable. It exhibits good loading and is user-friendly because of its free-flowing form upon drying. It performs excellently for the preparation of hydrophobic, highly structured, and poly-Arg peptides, as compared to polystyrene (PS) resins. In the most striking example, stepwise solid-phase assembly of the highly complex beta-amyloid (1-42) peptide resulted in a crude material of 91% purity. In contrast, literature procedures using PS or PEG-PS-based resins for this peptide required convergent approaches, additional time-consuming steps, or both. In addition to the difficulties of its synthesis, characterization of the beta-amyloid (1-42) peptide as a monomer is also a challenge, and methods for characterization by HPLC and MALDI-TOF have also been developed.
Garcia-Martin, Fayna Quintanar-Audelo, Martina Garcia-Ramos, Yesica Cruz, Luis J Gravel, Catherine Furic, Robert Cote, Simon Tulla-Puche, Judit Albericio, Fernando Research Support, Non-U.S. Gov't United States Journal of combinatorial chemistry J Comb Chem. 2006 Mar-Apr;8(2):213-20.
The following values have no corresponding Zotero field: auth-address: Barcelona Biomedical Research Institute, Barcelona Science Park, University of Barcelona, Josep Samitier 1, 08028-Barcelona, Spain. number: 2 edition: 2006/03/15 accession-num: 16529516
Keywords: Chromatography, High Pressure Liquid; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Peptides/*chemical synthesis; Spectrophotometry, Infrared; *Polyethylene Glycols; Amyloid beta-Peptides/*chemical synthesis; Drug Stability; Peptide Fragments/*chemical synthesis; Resins, Synthetic

Toward an intimate understanding of the structural properties and conformational preference of oxoesters and thioesters: Gas and crystal structure and conformational analysis of dimethyl monothiocarbonate, CH3OC(O)SCH3 - Erben, Mauricio F.; Boese, Roland; Della Védova, Carlos O.; Oberhammer, Heinz; Willner, Helge (J. Org. Chem., 2006)
doi: 10.1021/jo052026k 0022-3263 doi: 10.1021/jo052026k
The following values have no corresponding Zotero field: number: 2 publisher: American Chemical Society

Strategy for the synthesis of multivalent peptide-based nonsymmetric dendrimers by native chemical ligation - Dirksen, Anouk; Meijer, E. W.; Adriaens, Wencke; Hackeng, Tilman M. (Chem. Commun., 2006)
A strategy for the synthesis of multivalent peptide-based nonsymmetric dendrimers by native chemical ligation using poly(lysine) dendritic wedges as scaffolds is presented.
The following values have no corresponding Zotero field: number: 15 publisher: The Royal Society of Chemistry work-type: 10.1039/B600286B

Dynamic Combinatorial Chemistry - Corbett, Peter T.; Leclaire, Julien; Vial, Laurent; West, Kevin R.; Wietor, Jean-Luc; Sanders, Jeremy K. M.; Otto, Sijbren (Chem. Rev., 2014)
doi: 10.1021/cr020452p
The following values have no corresponding Zotero field: number: 9 publisher: American Chemical Society

Sugar-assisted glycopeptide ligation - Brik, A.; Yang, Y. Y.; Ficht, S.; Wong, C. H. (J. Am. Chem. Soc., 2006)
The chemical synthesis of glycopeptides and glycoproteins from readily available materials presents an attractive route to homogeneous products for structural and functional studies. Chemical synthesis of glycopeptides and glycoproteins based on native chemical ligation represents one of the useful methods for the synthesis of natural glycopeptide structures. Here we describe a method that allows for the synthesis of glycopeptides from cysteine-free peptides. This method utilizes a peptide thioester and a glycopeptide in which the sugar moiety is modified with a thiol handle at the C-2 position. Upon completion of the ligation reaction, the thiol handle can be reduced with H2/metal to the acetamide moiety, furnishing the unmodified glycopeptides. Together, this sequence of reactions displays an attractive potential in glycopeptides and glycoproteins synthesis.
0002-7863 (Print) 0002-7863 (Linking) Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Department of Chemistry and Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. number: 17 accession-num: 16637616
Keywords: Chromatography, High Pressure Liquid; Spectrometry, Mass, Electrospray Ionization; Carbohydrates/*chemistry; Glycopeptides/*chemistry

Sugar-assisted ligation of N-linked glycopeptides with broad sequence tolerance at the ligation junction - Brik, A.; Ficht, S.; Yang, Y.-Y.; Wong, C.-H. (J. Am. Chem. Soc., 2006)
null
doi: 10.1021/ja065601q 0002-7863 doi: 10.1021/ja065601q
The following values have no corresponding Zotero field: number: 46 publisher: American Chemical Society

Chemoselective amide ligations by decarboxylative condensations of N-alkylhydroxylamines and a-ketoacids - Bode, J. W.; Fox, R. M.; Baucom, K. D. (Angew. Chem. Int. Ed., 2006)
1433-7851 (Print) 1433-7851 (Linking) Journal Article
The following values have no corresponding Zotero field: auth-address: Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, USA. bode@chem.ucsb.edu number: 8 accession-num: 16416482

Kinetically controlled ligation for the convergent chemical synthesis of proteins - Bang, D.; Pentelute, B. L.; Kent, S. B. H. (Angew. Chem. Int. Ed., 2006)
1433-7851 (Print) 1433-7851 (Linking) Journal Article Research Support, U.S. Gov't, Non-P.H.S.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Institute for Biophysical Dynamics, Center for Integrative Science, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA. skent@uchicago.edu number: 24 accession-num: 16639756
Keywords: Kinetics; Peptides/*chemistry; Proteins/*chemical synthesis; Plant Proteins/*chemical synthesis

Direct on-resin synthesis of peptide-alpha thiophenylesters for use in native chemical ligation - Bang, D.; Pentelute, B. L.; Gates, Z. P.; Kent, S. B. H. (Org. Lett., 2006)
[reaction: see text] A peptide-(alpha)thiophenylester is a key reactant in native chemical ligation. Preformation of the peptide-(alpha)thiophenylester could be useful for enhancing the ligation reaction. We report the direct on-resin preparation of preformed peptide-(alpha)thiophenylesters using a simple and efficient method. The peptide-(alpha)thiophenylester reacted extremely rapidly with a Cys-peptide when compared to the peptide-(alpha)thioalkylester.
1523-7060 (Print) 1523-7052 (Linking) Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.
The following values have no corresponding Zotero field: auth-address: Institute for Biophysical Dynamics, Department of Chemistry, The University of Chicago, Chicago, Illinois 60637, USA. number: 6 accession-num: 16524265
Keywords: Amino Acid Sequence; Models, Molecular; Molecular Structure; Peptides/*chemical synthesis/chemistry; Molecular Sequence Data; Esters; Thermodynamics; Benzene Derivatives/*chemical synthesis/chemistry

One pot synthesis of selenocysteine containing peptoid libraries by Ugi multicomponent reactions in water - Abbas, Muhammad; Bethke, John; Wessjohann, Ludger A. (Chem. Commun., 2006)
Selenocysteine containing peptoids and peptide-peptoid conjugates were synthesized by combinatorial Ugi-MCRs (multicomponent reactions) in water: for the first time, an acetal (selenoacetal 2a) was used in Ugi-MCR to furnish selenocysteine peptoids in one step as model compounds for selenocysteine peptides and proteins.
The following values have no corresponding Zotero field: number: 5 publisher: The Royal Society of Chemistry work-type: 10.1039/B514597J

Photolabile protection for one-pot sequential native chemical ligation - Ueda, S.; Fujita, M.; Tamamura, H.; Fujii, N.; Otaka, A. (ChemBioChem, 2005)
1439-4227 (Print) 1439-4227 (Linking) Journal Article Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. number: 11 accession-num: 16206319
Keywords: Molecular Structure; Peptides/*chemical synthesis/chemistry; *Photolysis

Noncovalent binding between guanidinium and anionic groups: Focus on biological- and synthetic-based arginine/guanidinium interactions with phosph[on]ate and sulf[on]ate residues - Schug, Kevin A.; Lindner, Wolfgang (Chem. Rev., 2005)
doi: 10.1021/cr040603j 0009-2665 doi: 10.1021/cr040603j
The following values have no corresponding Zotero field: number: 1 publisher: American Chemical Society

Synthesis of the C-terminal region of opioid receptor like 1 in an SDS micelle by the native chemical ligation: effect of thiol additive and SDS concentration on ligation efficiency - Sato, T.; Saito, Y.; Aimoto, S. (J. Pept. Sci., 2005)
In the process of developing a method for the synthesis of membrane proteins, the conditions for native chemical ligation, namely, detergent concentration and the chemical characteristics of the thiol additive were investigated in detail. The C-terminal region of the opioid receptor like 1, ORL1(288-370), which contains C-terminal intracellular and transmembrane domains, was chosen as a model. The building blocks, ORL1(329-370) and ORL1(288-328)-SR-Gly-Arg(5)-Leu (-SR- : -SCH(2)CH(2)CO-) were most effectively condensed slightly below the critical micelle concentration of SDS and in the presence of mercaptoethanesulfonic acid as a thiol additive. The results showed that the concentration of SDS and the charge on the thiol additive are crucial factors for the effective synthesis of a membrane protein by native chemical ligation.
Journal Article Research Support, Non-U.S. Gov't England an official publication of the European Peptide Society
The following values have no corresponding Zotero field: auth-address: Institute for Protein Research, Osaka University, Osaka 565-0871, Japan. number: 7 accession-num: 15635671
Keywords: Amino Acid Sequence; Molecular Sequence Data; Chromatography, High Pressure Liquid; Amino Acids/chemistry; Sulfhydryl Compounds/*chemistry; Fluorenes/chemistry; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; *Micelles; *Sodium Dodecyl Sulfate; Arginine/metabolism; Mercaptoethanol/*analogs & derivatives/*chemistry; Peptide Fragments/*biosynthesis; Receptors, Opioid/*biosynthesis/chemistry/metabolism

Crystallographic trapping of the glutamyl-CoA thioester intermediate of family I CoA transferases - Rangarajan, E. S.; Li, Y.; Ajamian, E.; Iannuzzi, P.; Kernaghan, S. D.; Fraser, M. E.; Cygler, M.; Matte, A. (J. Biol. Chem., 2005)
Coenzyme A transferases are involved in a broad range of biochemical processes in both prokaryotes and eukaryotes, and exhibit a diverse range of substrate specificities. The YdiF protein from Escherichia coli O157:H7 is an acyl-CoA transferase of unknown physiological function, and belongs to a large sequence family of CoA transferases, present in bacteria to humans, which utilize oxoacids as acceptors. In vitro measurements showed that YdiF displays enzymatic activity with short-chain acyl-CoAs. The crystal structures of YdiF and its complex with CoA, the first co-crystal structure for any Family I CoA transferase, have been determined and refined at 1.9 and 2.0 A resolution, respectively. YdiF is organized into tetramers, with each monomer having an open alpha/beta structure characteristic of Family I CoA transferases. Co-crystallization of YdiF with a variety of CoA thioesters in the absence of acceptor carboxylic acid resulted in trapping a covalent gamma-glutamyl-CoA thioester intermediate. The CoA binds within a well defined pocket at the N- and C-terminal domain interface, but makes contact only with the C-terminal domain. The structure of the YdiF complex provides a basis for understanding the different catalytic steps in the reaction of Family I CoA transferases.
Journal Article Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: Department of Biochemistry, McGill University, Quebec, Canada. alt-title: The Journal of biological chemistry number: 52 accession-num: 16253988
Keywords: Models, Molecular; Protein Conformation; Molecular Conformation; Catalysis; Mass Spectrometry; Protein Structure, Quaternary; Protein Folding; Catalytic Domain; Esters/*chemistry; Protein Structure, Tertiary; Chromatography, Gel; Binding Sites; Models, Chemical; Protein Structure, Secondary; Carboxylic Acids/chemistry; Cloning, Molecular; Coenzyme A-Transferases/*chemistry/metabolism; Coenzyme A/*chemistry; Crystallization; Crystallography, X-Ray/*methods; Escherichia coli Proteins/*chemistry/metabolism; Escherichia coli/*enzymology/metabolism; Glutamic Acid/*chemistry; Histidine/chemistry

Synthesis of collagen-like peptide polymers by native chemical ligation - Paramonov, Sergey E.; Gauba, Varun; Hartgerink, Jeffrey D. (Macromolecules, 2005)
The following values have no corresponding Zotero field: number: 18 publisher: American Chemical Society

Fmoc solid-phase synthesis of peptide thioesters using an intramolecular N,S-acyl shift - Ollivier, N.; Behr, J. B.; El-Mahdi, O.; Blanpain, A.; Melnyk, O. (Org. Lett., 2005)
[reaction: see text] We describe the Fmoc solid-phase synthesis of peptide thioesters based on the alkylation of the safety-catch sulfonamide linker with a protected 2-mercaptoethanol derivative. The thioester is generated on the solid phase after the peptide chain assembly as a consequence of an intramolecular N,S-acyl shift. Depending on the stability of the spacer separating the sulfonamide linker from the resin toward TFA, treatment of the peptidyl resin with TFA led to a soluble or supported deprotected thioester.
1523-7060 (Print) 1523-7052 (Linking) Journal Article Research Support, Non-U.S. Gov't
The following values have no corresponding Zotero field: auth-address: Institut Pasteur de Lille, Universite de Lille 2, UMR 8525 CNRS, 1 rue du Professeur Calmette, 59021 Lille Cedex, France. number: 13 accession-num: 15957912
Keywords: Amino Acid Sequence; Molecular Sequence Data; Esters; Amino Acids/*chemistry; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Peptides/*chemical synthesis; *Combinatorial Chemistry Techniques

Intramolecular addition of cysteine thiyl radicals to phenylalanine in peptides: formation of cyclohexadienyl type radicals - Nauser, Thomas; Casi, Giulio; Koppenol, Willem H.; Schoneich, Christian (Chem. Commun., 2005)
The -molecular addition of peptide cysteine thiyl radicals to phenylalanine yields alkylthio-substituted cyclohexadienyl radicals for the peptides Phe-Cys and Phe-Gly-Cys-Gly, even when Phe and Cys are separated by a Gly residue, and presents a possible free radical pathway to thioether-containing peptide and protein cross-links.
1359-7345 10.1039/B506094J
The following values have no corresponding Zotero field: number: 27 publisher: The Royal Society of Chemistry

Isosteric replacement of sulfur with other chalcogens in peptides and proteins - Moroder, L. (J. Pept. Sci., 2005)
The review addresses the functional and structural properties of the two series of chalcogen analogues of amino acids in peptides and proteins, the methionine and the serine/cysteine series, and discusses the synthesis of the related selenium/tellurium analogues as well as their use in peptide synthesis and protein expression. Advances in synthetic methodologies and recombinant technologies and their combined applications in native and expressed protein ligation allows the isomorphous character of selenium- and tellurium-containing amino acids to be exploited for production of heavy metal mutants of proteins and thus to facilitate the phasing problem in x-ray crystallography. In addition, selenocysteine has been recognized as an ideal tool for the production of selenoenzymes with new catalytic activities. Moreover, the fully isomorphous character of disulfide replacement with diselenide is well suited to increase the robustness of cystine frameworks in cystine-rich peptides and proteins and for the de novo design of even non-native cystine frameworks by exploiting the highly negative redox potential of selenols.
1075-2617 (Print) 1075-2617 (Linking) Journal Article Review
The following values have no corresponding Zotero field: auth-address: Max-Planck-Institut fur Biochemie, D-82152 Martinsried, Germany. moroder@biochem.mpg.de number: 4 accession-num: 15782428
Keywords: Models, Molecular; Proteins/*chemical synthesis/chemistry; Cysteine/chemistry; Peptides/*chemical synthesis/chemistry; Crystallography, X-Ray; Serine/chemistry; Sulfur/*chemistry; Selenium/chemistry; Chalcogens/*chemistry; Methionine/chemistry; Tellurium/chemistry

An orthogonal double-linker resin facilitates the efficient solid-phase synthesis of complex-type N-glycopeptide thioesters suitable for native chemical ligation - Mezzato, S.; Schaffrath, M.; Unverzagt, C. (Angew. Chem. Int. Ed., 2005)
Mezzato, Stefano Schaffrath, Manuela Unverzagt, Carlo Germany International ed. in English Angew Chem Int Ed Engl. 2005 Mar 4;44(11):1650-4.
The following values have no corresponding Zotero field: auth-address: Bioorganische Chemie, Gebaude NW1, Universitat Bayreuth, 95440 Bayreuth, Germany. number: 11 edition: 2005/02/05 accession-num: 15693053 work-type: Research Support, Non-U.S. Gov't
Keywords: Protein Conformation; Molecular Sequence Data; Chromatography, High Pressure Liquid; Mass Spectrometry; Esters; Glycosylation; Carbohydrate Sequence; Glycopeptides/*chemical synthesis

Mechanistic investigation of the staudinger ligation - Lin, F. L.; Hoyt, H. M.; van Halbeek, H.; Bergman, R. G.; Bertozzi, C. R. (J. Am. Chem. Soc., 2005)
The Staudinger ligation of azides and phosphines has found widespread use in the field of chemical biology, but the mechanism of the transformation has not been characterized in detail. In this work, we undertook a mechanistic study of the Staudinger ligation with a focus on factors that affect reaction kinetics and on the identification of intermediates. The Staudinger ligation with alkyl azides was second-order overall and proceeded more rapidly in polar, protic solvents. Hammett analyses demonstrated that electron-donating substituents on the phosphine accelerate the overall reaction. The electronic and steric properties of the ester had no significant impact on the overall rate but did affect product ratios. Finally, the structure of an intermediate that accumulates under anhydrous conditions was identified. These findings establish a platform for optimizing the Staudinger ligation for expanded use in biological applications.
0002-7863 (Print) 0002-7863 (Linking) Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Howard Hughes Medical Institute, University of California, and Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA. number: 8 accession-num: 15725026
Keywords: Kinetics; Structure-Activity Relationship; Azides/*chemistry; Solvents; Phosphines/*chemistry; Magnetic Resonance Spectroscopy/methods; Phosphorus

Expanding diversity in dynamic combinatorial libraries: simultaneous exchange of disulfide and thioester linkages - Leclaire, Julien; Vial, Laurent; Otto, Sijbren; Sanders, Jeremy K. M. (Chem. Commun., 2005)
Dynamic combinatorial libraries have been prepared which feature two simultaneous covalent exchange reactions in aqueous solution at neutral pH. This allows for diversity, not only of the subunits that are linked, but also of the linkage itself.
The following values have no corresponding Zotero field: number: 15 publisher: The Royal Society of Chemistry work-type: 10.1039/B500638D

(untitled) - Hratchian, H. P.; Schlegel, H. B. (Theory and Applications of Computational Chemistry: The First 40 Years, 2005)
Keywords: #nosource

Incorporation of selenocysteine into proteins using peptide ligation - Hondal, R. J. (Protein Pept Lett, 2005)
Expressed protein ligation has become a frequently used technique to insert non-standard amino acids into proteins. The technique has been adapted to insert selenocysteine residues in place of cysteine residue in proteins, taking advantage of the similarity in the chemistries of sulfur and selenium. This replacement can confer unique structural and catalytic properties to enzymes and proteins. The development of this technique also allows for naturally occurring selenoproteins to be produced semisynthetically.
0929-8665 (Print) 0929-8665 (Linking) Journal Article Research Support, N.I.H., Extramural Review
The following values have no corresponding Zotero field: auth-address: Department of Biochemistry, Vermont College of Medicine, The University of Vermont, Burlington, VT 05405, USA. Robert.Hondal@uvm.edu number: 8 accession-num: 16305545
Keywords: Animals; Humans; Chromatography, High Pressure Liquid; Proteins/*chemistry; Peptides/chemical synthesis/*chemistry; Models, Chemical; Inteins; Biochemistry/*methods; Ribonucleases/chemistry/genetics; Selenocysteine/chemical synthesis/*chemistry; Thioredoxin-Disulfide Reductase/chemical synthesis/chemistry

N-Acyl-N-alkyl-sulfonamide anchors derived from Kenner’s safety-catch linker: powerful tools in bioorganic and medicinal chemistry - Heidler, Philipp; Link, Andreas (Bioorg. Med. Chem., 2005)
In 1971 Kenner et al. introduced the safety-catch principle into solid phase peptide synthesis. Thus two contradicting needs were addressed. On the one hand, sufficient stability of the linker substrate bond to impede hydrolysis or similar side reactions, on the other hand mild chemical conditions allowing for unscathed liberation of the precious products. Over the years this linker type emerged in several different chemical disciplines and nowadays it presents a useful and broadly applicable tool. Recent advancements and applications based on Kenner’s safety-catch linker are reviewed.
The following values have no corresponding Zotero field: number: 3

Preparation of protected peptidyl thioester intermediates for native chemical ligation by Na-9-fluorenylmethoxycarbonyl (Fmoc) chemistry: considerations of side-chain and backbone anchoring strategies, and compatible protection for N-terminal cysteine - Gross, C. M.; Lelievre, D.; Woodward, C. K.; Barany, G. (J. Pept. Res., 2005)
Native chemical ligation has proven to be a powerful method for the synthesis of small proteins and the semisynthesis of larger ones. The essential synthetic intermediates, which are C-terminal peptide thioesters, cannot survive the repetitive piperidine deprotection steps of N(alpha)-9-fluorenylmethoxycarbonyl (Fmoc) chemistry. Therefore, peptide scientists who prefer to not use N(alpha)-t-butyloxycarbonyl (Boc) chemistry need to adopt more esoteric strategies and tactics in order to integrate ligation approaches with Fmoc chemistry. In the present work, side-chain and backbone anchoring strategies have been used to prepare the required suitably (partially) protected and/or activated peptide intermediates spanning the length of bovine pancreatic trypsin inhibitor (BPTI). Three separate strategies for managing the critical N-terminal cysteine residue have been developed: (i) incorporation of N(alpha)-9-fluorenylmethoxycarbonyl-S-(N-methyl-N-phenylcarbamoyl)sulfenyl cysteine [Fmoc-Cys(Snm)-OH], allowing creation of an otherwise fully protected resin-bound intermediate with N-terminal free Cys; (ii) incorporation of N(alpha)-9-fluorenylmethoxycarbonyl-S-triphenylmethylcysteine [Fmoc-Cys(Trt)-OH], generating a stable Fmoc-Cys(H)-peptide upon acidolytic cleavage; and (iii) incorporation of N(alpha)-t-butyloxycarbonyl-S-fluorenylmethylcysteine [Boc-Cys(Fm)-OH], generating a stable H-Cys(Fm)-peptide upon cleavage. In separate stages of these strategies, thioesters are established at the C-termini by selective deprotection and coupling steps carried out while peptides remain bound to the supports. Pilot native chemical ligations were pursued directly on-resin, as well as in solution after cleavage/purification.
1397-002X (Print) 1397-002X (Linking) Journal Article
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA. number: 3 accession-num: 15787970
Keywords: Amino Acid Sequence; Cysteine/*chemistry; Molecular Sequence Data; Amino Acids/*chemical synthesis/*chemistry; Aprotinin/chemical synthesis/chemistry; Fluorenes/*chemical synthesis/*chemistry; Peptide Fragments/*chemical synthesis/*chemistry; Sulfur Compounds/chemical synthesis/chemistry

Synthesis of lipidated green fluorescent protein and its incorporation in supported lipid bilayers - Grogan, M. J.; Kaizuka, Y.; Conrad, R. M.; Groves, J. T.; Bertozzi, C. R. (J. Am. Chem. Soc., 2005)
Herein we report a semisynthetic method of producing membrane-anchored proteins. Ligation of synthetic lipids with designed anchor structures to proteins was performed using native chemical ligation (NCL) of a C-terminal peptide thioester and an N-terminal cysteine lipid. This strategy mimics the natural glycosylphosphatidylinositol (GPI) linkage found in many natural membrane-associated proteins; however, the synthetic method utilizes simple lipid anchors without glycans. Synthetically lipidated recombinant green fluorescent protein (GFP) was shown to be stably anchored to the membrane, and its lateral fluidity was quantitatively characterized by direct fluorescence imaging in supported membranes. Circumventing the steps of purification from native cell membranes, this methodology facilitates the reconstitution of membrane-associated proteins.
Grogan, Michael J Kaizuka, Yoshihisa Conrad, Rosemary M Groves, Jay T Bertozzi, Carolyn R J Am Chem Soc. 2005 Oct 19;127(41):14383-7.
The following values have no corresponding Zotero field: auth-address: Departments of Chemistry and Molecular and Cell Biology, Physical Biosciences and Materials Sciences Divisions, University of California-Berkeley, Berkeley, CA 94720, USA. alt-title: Journal of the American Chemical Society number: 41 edition: 2005/10/13 accession-num: 16218633 work-type: Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.
Keywords: Molecular Structure; Green Fluorescent Proteins/*chemical synthesis/chemistry; Lipid Bilayers/*chemical synthesis/chemistry; Lipids/*chemistry

Effects of redox buffer properties on the folding of a disulfide-containing protein: dependence upon pH, thiol pKa, and thiol concentration - Gough, J. D.; Lees, W. J. (J. Biotechnol., 2005)
Aliphatic thiols are effective as redox buffers for folding non-native disulfide-containing proteins into their native state at high pH values (8.0-8.5) but not at neutral pH values (6-7.5). In developing more efficient and flexible redox buffers, a series of aromatic thiols was analyzed for its ability to fold scrambled ribonuclease A (sRNase A). At equivalent pH values, the aromatic thiols folded sRNase A 10-23 times faster at pH 6.0, 7-12 times faster at pH 7.0, and 5-8 times faster at pH 7.7 than the standard aliphatic thiol glutathione. Similar correlations between thiol pK(a) values and folding rates at each pH value suggest that the apparent folding rate constants (k(app)) are a function of the redox buffer properties (pH, thiol pK(a) and [RSH]). Fitting the observed data to a three-variable model (logk(app)=-4.216(+/-0.030)+0.5816(+/-0.0036)pH-0.233(+/-0.004)pK(a)+log(1-e(-0.9 8(+/-0.02)[RSH]))) gave good statistics: r2=0.915, s=0.10.
Comparative Study Evaluation Studies Journal Article Research Support, U.S. Gov't, Non-P.H.S. Netherlands
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Syracuse University, Syracuse, NY 13244, USA. alt-title: Journal of biotechnology number: 3 accession-num: 15639090
Keywords: Protein Conformation; Kinetics; Hydrogen-Ion Concentration; *Models, Molecular; Sulfhydryl Compounds/*chemistry; Oxidation-Reduction; Protein Folding; Disulfides/*chemistry; Computer Simulation; Buffers; Protein Denaturation; *Models, Chemical; Ribonuclease, Pancreatic/analysis/*chemistry

Synthesis of glyoxylyl peptides using an Fmoc-protected alpha,alpha'-diaminoacetic acid derivative - Far, S.; Melnyk, O. (J. Pept. Sci., 2005)
The synthesis of glyoxylyl peptides by coupling the masked glyoxylic acid derivative (FmocNH)(2)CHCO(2)H, 1, to a peptidyl resin assembled using Fmoc/tert-butyl chemistry has been described recently. Deprotection and cleavage of the peptide from the solid support using TFA was followed by unmasking of the glyoxylyl group in solution in the presence of DBU. [] The glyoxylyl peptide was thus generated using non-oxidizing conditions by comparison with the method based on the periodic oxidation of a seryl-precursor. However, base treatment of the (FmocNH)(2)CHCO(2)-peptide led to the formation of a byproduct besides the desired glyoxylyl peptide. This paper describes an optimized procedure for unmasking the Fmoc-protected alpha,alpha'-diaminoacetic acid moiety in solution which suppressed byproduct formation. Also presented is a series of experiments that permitted a structure and a mechanism of formation for the byproduct to be suggested.
Journal Article Research Support, Non-U.S. Gov't England an official publication of the European Peptide Society
The following values have no corresponding Zotero field: auth-address: UMR 8525 CNRS-Universite de Lille 2, Institut de Biologie de Lille, 1 rue du Professeur Calmette, 59021 Lille, France. number: 7 accession-num: 15641117
Keywords: Peptides/*chemical synthesis/chemistry; Amino Acids/*chemistry; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Fluorenes/*chemistry; Acetates/*metabolism; Amino Acids, Diamino/*metabolism; Glyoxylates/*metabolism; Hydroxylamines/metabolism

A novel phosphoramidite for the synthesis of a-oxo aldehyde-modified oligodeoxynucleotides - Far, Samia; Gouyette, Catherine; Melnyk, Oleg (Tetrahedron, 2005)
The synthesis and use of a novel phosphoramidite derivatized by a bis[2-(tert-butyldisulfanyl)ethoxycarbonylamino]acetyl moiety for the synthesis of oligodeoxynucleotides modified at the 5′-end by an α-oxo aldehyde functionality is presented. Incorporation of the phosphoramidite reagent was performed after the automated solid-phase oligonucleotide synthesis. Simultaneous cleavage/deprotection of the oligodeoxynucleotides and unmasking of the α-oxo aldehyde group could be achieved using NaOH in aqueous methanol in the presence of dithiothreitol.
0040-4020
The following values have no corresponding Zotero field: number: 25
Keywords: Alpha-oxo aldehyde; DTT; Oligodeoxynucleotide; Phosphoramidite

Granulysin, a cytolytic molecule, is also a chemoattractant and proinflammatory activator - Deng, A.; Chen, S.; Li, Q.; Lyu, S. C.; Clayberger, C.; Krensky, A. M. (J. Immunol., 2005)
Granulysin, a cationic protein produced by activated human CTL and NK cells, is cytolytic against microbial and tumor targets. In this study we show that granulysin also functions as a chemoattractant and activates monocytes to produce cytokines/chemokines. Although granulysin-mediated cytotoxicity occurs at micromolar concentrations, chemoattraction occurs in the nanomolar range, and immune activation occurs over a wide range of concentrations (nanomolar to micromolar). Granulysin causes a 2- to 7-fold increase in chemotaxis of monocytes, CD4(+), and CD8(+) memory (CD45RO) but not naive (CD45RA) T cells, NK cells, and mature, but not immature, monocyte-derived dendritic cells. Pertussis toxin treatment abrogates chemoattraction by granulysin, indicating involvement of G-protein-coupled receptor(s). At low concentrations (10 nM), granulysin promotes a 3- to 10-fold increase in MCP-1 and RANTES produced by monocytes and U937 cells, while a 2-fold increase in TNF-alpha production by LPS-stimulated monocytes requires higher concentrations of granulysin (micromolar). Taken together, these data indicate that the local concentration of granulysin is critical for the biologic activity, with high concentrations resulting in cytotoxicity while lower concentrations, presumably further from the site of granulysin release, actively recruit immune cells to sites of inflammation.
Deng, Anmei Chen, Sunxiao Li, Qing Lyu, Shu-Chen Clayberger, Carol Krensky, Alan M AI43348/AI/NIAID NIH HHS/ Baltimore, Md. : 1950 J Immunol. 2005 May 1;174(9):5243-8.
The following values have no corresponding Zotero field: auth-address: Division of Immunology and Transplantation Biology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA. number: 9 edition: 2005/04/22 accession-num: 15843520 work-type: Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.
Keywords: Humans; Cell Line; *Cytotoxicity, Immunologic; Antigens, Differentiation, T-Lymphocyte/*physiology/*toxicity; B-Lymphocytes/immunology/pathology; Cell Migration Inhibition; Chemotactic Factors/*physiology/toxicity; Chemotaxis, Leukocyte/immunology; Dendritic Cells/immunology/pathology; Inflammation Mediators/*physiology/toxicity; Killer Cells, Natural/immunology/pathology; Monocytes/immunology/pathology; Pertussis Toxin/pharmacology; Recombinant Proteins/antagonists & inhibitors/pharmacology/toxicity; T-Lymphocytes/immunology/pathology; U937 Cells

Development and validation of spectrophotometric methods for determination of fluoxetine, sertraline, and paroxetine in pharmaceutical dosage forms - Darwish, I. A. (J AOAC Int, 2005)
Three simple and sensitive spectrophotometric methods were developed and validated for determination of the hydrochloride salts of fluoxetine, sertraline, and paroxetine in their pharmaceutical dosage forms. These methods were based on the reaction of the N-alkylvinylamine formed from the interaction of the free secondary amino group in the investigated drugs and acetaldehyde with each of 3 haloquinones, i.e., chloranil, bromanil, and 2,3-dichloronaphthoquinone, to give colored vinylamino-substituted quinones. The colored products obtained with chloranil, bromanil, and 2,3-dichloronaphthoquinone exhibit absorption maxima at 665, 655, and 580 nm, respectively. The factors affecting the reactions were studied and optimized. Under the optimum reaction conditions, linear relationships with good correlation coefficients (0.9986-0.9999) were found between the absorbances and the concentrations of the investigated drugs in the range of 4-120 microg/mL. The limits of detection for the assays ranged from 1.19 to 2.98 microg/mL. The precision values of the methods were satisfactory; the relative standard deviations were 0.56-1.24%. The proposed methods were successfully applied to the determination of the 3 drugs in pure and pharmaceutical dosage forms with good accuracy; the recoveries ranged from 99.1 to 101.3% with standard deviations of 1.15-1.92%. The results compared favorably with those of reported methods.
Darwish, Ibrahim A United States Journal of AOAC International J AOAC Int. 2005 Jan-Feb;88(1):38-45.
The following values have no corresponding Zotero field: auth-address: Assiut University, Faculty of Pharmacy, Department of Pharmaceutical Analytical Chemistry, Assiut 71526, Egypt. iadarwish@yahoo.com number: 1 edition: 2005/03/12 accession-num: 15759724
Keywords: Dose-Response Relationship, Drug; Time Factors; Models, Chemical; Sensitivity and Specificity; *Pharmaceutical Preparations; Acetaldehyde/chemistry; Benzoquinones/*analysis; Chemistry Techniques, Analytical/*methods; Chloranil/chemistry; Fluoxetine/*analysis; Naphthoquinones/chemistry; Paroxetine/*analysis; Phenanthrenes/chemistry; Quality Control; Quinones/chemistry; Serotonin Uptake Inhibitors/*analysis; Sertraline/*analysis; Spectrophotometry/*methods

Practical asymmetric preparation of azetidine-2-carboxylic Acid - Couty, Francois; Evano, Gwilherm; Vargas-Sanchez, Monica; Bouzas, Gloria (J. Org. Chem., 2005)
doi: 10.1021/jo0515881 0022-3263 doi: 10.1021/jo0515881
The following values have no corresponding Zotero field: number: 22 publisher: American Chemical Society

Synthetic erythropoietic proteins: tuning biological performance by site-specific polymer attachment - Chen, S. Y.; Cressman, S.; Mao, F.; Shao, H.; Low, D. W.; Beilan, H. S.; Cagle, E. N.; Carnevali, M.; Gueriguian, V.; Keogh, P. J.; Porter, H.; Stratton, S. M.; et al. (Chem. Biol., 2005)
Chemical synthesis in combination with precision polymer modification allows the systematic exploration of the effect of protein properties, such as charge and hydrodynamic radius, on potency using defined, homogeneous conjugates. A series of polymer-modified synthetic erythropoiesis proteins were constructed that had a polypeptide chain similar to the amino acid sequence of human erythropoietin but differed significantly in the number and type of attached polymers. The analogs differed in charge from +5 to -26 at neutral pH and varied in molecular weight from 30 to 54 kDa. All were active in an in vitro cell proliferation assay. However, in vivo potency was found to be strongly dependent on overall charge and size. The trends observed in this study may serve as starting points for the construction of more potent synthetic EPO analogs in the future.
Journal Article United States
The following values have no corresponding Zotero field: auth-address: Gryphon Therapeutics, 600 Gateway Boulevard, South San Francisco, California 94080, USA. alt-title: Chemistry & biology number: 3 accession-num: 15797221
Keywords: Amino Acid Sequence; Animals; Humans; Dose-Response Relationship, Drug; Molecular Sequence Data; Mice; Cell Proliferation/drug effects; Rats; Binding Sites/drug effects/physiology; Erythropoiesis/*physiology; Erythropoietin/chemical synthesis/metabolism/physiology; Macaca fascicularis; Polymers/*chemical synthesis/metabolism/pharmacology; Proteins/*chemical synthesis/metabolism/physiology

An unprecedented concerted pathway in the alkaline hydrolysis of S-aryl thioesters - Cevasco, Giorgio; Thea, Sergio (J. Org. Chem., 2005)
doi: 10.1021/jo050262p 0022-3263 doi: 10.1021/jo050262p
The following values have no corresponding Zotero field: number: 10 publisher: American Chemical Society

His6 tag-assisted chemical protein synthesis - Bang, D.; Kent, S. B. H. (Proc. Natl. Acad. Sci. U. S. A., 2005)
To make more practical the total chemical synthesis of proteins by the ligation of unprotected peptide building blocks, we have developed a method to facilitate the isolation and handling of intermediate products. The synthetic technique makes use of a His6 tag at the C terminus of the target polypeptide chain, introduced during the synthesis of the C-terminal peptide segment building block. The presence of a His6 tag enables the isolation of peptide or protein products directly from ligation reaction mixtures by Ni-NTA affinity column purification. This simple approach enables facile buffer exchange to alternate reaction conditions and is compatible with direct analytical control by protein MS of the multiple ligation steps involved in protein synthesis. We used syntheses of crambin and a modular tetratricopeptide repeat protein of 17 kDa as models to examine the utility of this affinity purification approach. The results show that His6 tag-assisted chemical protein synthesis is a useful method that substantially reduces handling losses and provides for rapid chemical protein syntheses.
Journal Article Research Support, U.S. Gov't, Non-P.H.S. United States
The following values have no corresponding Zotero field: auth-address: Institute for Biophysical Dynamics and Department of Chemistry, University of Chicago, Chicago, IL 60637, USA. alt-title: Proceedings of the National Academy of Sciences of the United States of America number: 14 accession-num: 15784744
Keywords: Amino Acid Sequence; Proteins/*chemical synthesis/chemistry; Molecular Sequence Data; Thermodynamics; Circular Dichroism; Protein Folding; Ligands; Models, Chemical; Histidine/chemistry; Oligopeptides/chemical synthesis/chemistry; Plant Proteins/chemical synthesis/chemistry; Repetitive Sequences, Amino Acid