The total synthesis of proteins by chemical route and the discovery of proteins of interest for tissue regeneration - Melnyk, O.; Agouridas, V.; Vicogne, J. (Actualite Chimique, 2017)
Export Date: 25 May 2018
Export Date: 25 May 2018
Export Date: 25 May 2018
Export Date: 25 May 2018
Export Date: 26 June 2019
Keywords: #nosource

A statistical view of protein chemical synthesis using NCL and extended methodologies - Agouridas, V.; El Mahdi, O.; Cargoët, M.; Melnyk, O. (Bioorganic and Medicinal Chemistry, 2017)
Cited By :2
Cited By :2
Cited By :2
Cited By :12
Export Date: 25 May 2018

From protein total synthesis to peptide transamidation and metathesis: playing with the reversibility of N,S-acyl or N,Se-acyl migration reactions - Melnyk, O.; Agouridas, V. (Current Opinion in Chemical Biology, 2014)
Cited By :15
Cited By :15
Cited By :15
Cited By :21
Export Date: 25 May 2018
Keywords: #nosource

Cesium carbonate mediated aryl triflate esters' deprotection - Green, A.E.; Agouridas, V.; Deniau, E. (Tetrahedron Letters, 2013)
Cited By :6
Cited By :6
Cited By :6
Export Date: 25 May 2018
Export Date: 25 May 2018
Keywords: #nosource

Conception, synthesis, and biological evaluation of original discodermolide analogues - De Lemos, E.; Agouridas, E.; Sorin, G.; Guerreiro, A.; Commerçon, A.; Pancrazi, A.; Betzer, J.-F.; Lannou, M.-I.; Ardisson, J. (Chemistry - A European Journal, 2011)
Cited By :9
Cited By :10
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Export Date: 26 June 2019
Keywords: #nosource

A highly diastereoselective synthesis of isoindolinone-centered Meyers' tetracyclic lactams. Application to the asymmetric synthesis of 3-alkylisoindolinones - Agouridas, V.; Capet, F.; Couture, A.; Deniau, E.; Grandclaudon, P. (Tetrahedron Asymmetry, 2011)
Cited By :10
Cited By :12
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Export Date: 26 June 2019
Keywords: #nosource

A concise and flexible diastereoselective approach to heteroring-fused isoindolinones - Ahn, G.; Lorion, M.; Agouridas, V.; Couture, A.; Deniau, E.; Grandclaudon, P. (Synthesis, 2011)
Cited By :4
Cited By :5
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Export Date: 26 June 2019
Keywords: #nosource

Synthesis and cytotoxic evaluation of cis-locked and constrained analogues of combretastatin and combretastatin A4 - Lorion, M.; Agouridas, V.; Couture, A.; Deniau, E.; Grandclaudon, P. (Tetrahedron Letters, 2010)
Cited By :9
Cited By :10
Export Date: 25 May 2018
Export Date: 26 June 2019
Keywords: #nosource

Cyclic sulfamidates as vehicles for the synthesis of poly- and diversely substituted benzosultams via unusual S(O)2-O bond cleavage - Lorion, M.; Agouridas, V.; Couture, A.; Deniau, E.; Grandclaudon, P. (Organic Letters, 2010)
Cited By :16
Cited By :18
Export Date: 25 May 2018
Export Date: 26 June 2019
Keywords: #nosource

Effect of fluorination on the pharmacological profile of 11β isomers of fulvestrant in breast carcinoma cells - Agouridas, V.; Magnier, E.; Blazejewski, J.-C.; Laïos, I.; Cleeren, A.; Nonclercq, D.; Laurent, G.; Leclercq, G. (Journal of Medicinal Chemistry, 2009)
Cited By :7
Cited By :8
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Keywords: #nosource

Total synthesis of discodermolide: Optimization of the effective synthetic route - De Lemos, E.; Porée, F.-H.; Bourin, A.; Barbion, J.; Agouridas, E.; Lannou, M.-I.; Commerçon, A.; Betzer, J.-F.; Pancrazi, A.; Ardisson, J. (Chemistry - A European Journal, 2008)
Cited By :22
Cited By :26
Export Date: 25 May 2018
Export Date: 26 June 2019
Keywords: #nosource

Design and synthesis of ansamycin antibiotics - Wrona, I.E.; Agouridas, V.; Panek, J.S. (Comptes Rendus Chimie, 2008)
Cited By :25
Cited By :27
Export Date: 25 May 2018
Export Date: 26 June 2019
Keywords: #nosource

Fluorous tolerance of the estrogen receptor alpha as probed by 11-polyfluoroalkylestradiol derivatives - Agouridas, V.; Blazejewski, J.-C.; Cleeren, A.; Laïos, I.; Leclercq, G.; Magnier, E. (Steroids, 2008)
Cited By :7
Cited By :7
Export Date: 25 May 2018
Export Date: 26 June 2019
Keywords: #nosource

Loss of antagonistic activity of tamoxifen by replacement of one N-methyl of its side chain by fluorinated residues - Agouridas, V.; Laïos, I.; Cleeren, A.; Kizilian, E.; Magnier, E.; Blazejewski, J.-C.; Leclercq, G. (Bioorganic and Medicinal Chemistry, 2006)
Cited By :18
Cited By :18
Export Date: 25 May 2018
Export Date: 26 June 2019
Keywords: #nosource

Synthesis of 11β-perfluorohexylestradiol - Agouridas, V.; Blazejewski, J.-C.; Magnier, E.; Popkin, M.E. (Journal of Organic Chemistry, 2005)
Cited By :8
Cited By :8
Export Date: 25 May 2018
Export Date: 26 June 2019
Keywords: #nosource

Traceless b-mercaptan-assisted activation of valinyl benzimidazolinones in peptide ligations - Wang, Yinglu; Han, Lin; Yuan, Ning; Wang, Hanxuan; Li, Hongxing; Liu, Jinrong; Chen, Huan; Zhang, Qiang; Dong, Suwei (Chem. Sci., 2018)
Peptidyl thioesters or their surrogates with C-terminal [small beta]-branched hydrophobic amino acid residues usually exhibit poor reactivities in ligation reactions. Thus, activation using exogenous additives is required to ensure an acceptable reaction efficiency. Herein, we report a traceless ligation at Val-Xaa sites under mild thiol additive-free reaction conditions, whereby the introduction of [small beta]-mercaptan on the C-terminal valine residue effectively activates the otherwise unreactive N-acyl-benzimidazolinone (Nbz), and enables the use of a one-pot ligation-desulfurization strategy to generate the desired peptide products. The orthogonality between [small beta]-thiovaline-Nbz and a conventional alkyl thioester, as well as the convenient access to the former from readily available penicillamine, also allowed expedited assembly of the peptidic hormone [small beta]-LPH and hPTH analogues, based on a kinetically controlled one-pot three-segment ligation and desulfurization strategy.
The following values have no corresponding Zotero field: number: 7 publisher: The Royal Society of Chemistry work-type: 10.1039/C7SC04148A

Easy-to-attach/detach solubilizing-tag-aided chemical synthesis of an aggregative capsid protein - Tsuda, Shugo; Mochizuki, Masayoshi; Ishiba, Hiroyuki; Yoshizawa-Kumagaye, Kumiko; Nishio, Hideki; Oishi, Shinya; Yoshiya, Taku (Angew. Chem. Int. Ed., 2018)
A solubilizing Trt-K10 tag was developed for the effective chemical preparation of peptides/proteins with low solubility. The Trt-K10 tag comprises a hydrophilic oligo-Lys sequence and a trityl anchor, and can be selectively introduced to a side chain thiol of Cys of deprotected peptides/proteins with a trityl alcohol-type introducing reagent Trt(OH)-K10 under acidic conditions. Significantly, the ligation product in the reaction mixture of a thiol-additive-free native chemical ligation can be modified directly in a one-pot manner to facilitate the isolation of the product by high-performance liquid chromatography. Finally, the Trt-K10 tag can be readily removed with a standard trifluoroacetic acid cocktail. Using this easy-to-attach/detach tag-aided method, a hepatitis B virus capsid protein that is usually difficult to handle was synthesized successfully.
The following values have no corresponding Zotero field: number: 8
Keywords: capsid proteins; native chemical ligation; peptide synthesis; solubilizing tags; Trt-K10

Peptide nucleic acid-templated selenocystine-selenoester ligation enables rapid miRNA detection - Sayers, Jessica; Payne, Richard J.; Winssinger, Nicolas (Chem. Sci., 2018)
The development of a rapid and chemoselective selenocystine-selenoester peptide ligation that operates at nanomolar reactant concentrations has been developed by utilising PNA templation. Kinetic analysis of the templated peptide ligation revealed that the selenocystine-selenoester reaction was 10 times faster than traditional native chemical ligation at cysteine and to our knowledge is the fastest templated ligation reaction reported to date. The efficiency and operational simplicity of this technology is highlighted through the formation of hairpin molecular architectures and in a novel paper-based lateral flow assay for the rapid and sequence specific detection of oligonucleotides, including miRNA in cell lysates.
The following values have no corresponding Zotero field: publisher: The Royal Society of Chemistry work-type: 10.1039/C7SC02736B

Chemical proteomic profiling of protein N-homocysteinylation with a thioester probe - Chen, Nan; Liu, Jinmin; Qiao, Zeyu; Liu, Yuan; Yang, Yue; Jiang, Changtao; Wang, Xian; Wang, Chu (Chem. Sci., 2018)
Hyperhomocysteinemia (HHcy) refers to a medical condition of abnormally high level of homocysteine (Hcy) in blood (>15 [small mu ]mol L-1) and has been clinically implicated with cardiovascular diseases and neurodegenerative disorders. Excessive Hcy can be converted to a reactive thioester intermediate, Hcy thiolactone (HTL), which selectively reacts with protein lysine residues ("N-homocysteinylation") and this non-enzymatic modification largely contributes to manifestations of HHcy. However, the proteome-wide detection of protein N-homocysteinylation remains a challenge to date. In this work, we report a chemoselective reaction to label and enrich N-homocysteinylation from complex proteome samples as inspired by native chemical ligation for protein synthesis. Alkynyl thioester probes are synthesized and the reaction is validated with small molecule and purified protein models successfully. We performed quantitative chemical proteomics to identify more than 800 N-homocysteinylated proteins as well as 304 N-homocysteinylated sites directly from HTL-treated HeLa cells. The chemical proteomics strategies will facilitate functional study of protein N-homocysteinylations in the HHcy-implicated diseases.
The following values have no corresponding Zotero field: publisher: The Royal Society of Chemistry work-type: 10.1039/C8SC00221E

Chemical synthesis of membrane proteins: a model study on the influenza virus B proton channel - Baumruck, A. C.; Tietze, D.; Steinacker, L. K.; Tietze, A. A. (Chem. Sci., 2018)
In the present study we have developed and optimized a robust strategy for the synthesis of highly hydrophobic peptides, especially membrane proteins, exemplarily using the influenza B M2 proton channel (BM2(1-51)). This strategy is based on the native chemical ligation of two fragments, where the thioester fragment is formed from an oxo-ester peptide, which is synthesized using Fmoc-SPPS, and features an in situ cleavable solubilizing tag (ADO, ADO2 or ADO-Lys5). The nearly quantitative production of the ligation product was followed by an optimized work up protocol, resulting in almost quantitative desulfurization and Acm-group cleavage. Circular dichroism analysis in a POPC lipid membrane revealed that the synthetic BM2(1-51) construct adopts a helical structure similar to that of the previously characterized BM2(1-33).
The following values have no corresponding Zotero field: number: 8 publisher: The Royal Society of Chemistry work-type: 10.1039/C8SC00004B

Recent advances in racemic protein crystallography - Yan, Bingjia; Ye, Linzhi; Xu, Weiliang; Liu, Lei (Bioorg. Med. Chem., 2017)
The following values have no corresponding Zotero field: auth-address: Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China. alt-title: Bioorg Med Chem number: 18 accession-num: 28705433

Abundance and functional roles of intrinsic disorder in the antimicrobial peptides of the NK-lysin family - Yacoub, H. A.; Al-Maghrabi, O. A.; Ahmed, E. S.; Uversky, V. N. (J. Biomol. Struct. Dyn., 2017)
NK-lysins are antimicrobial peptides (AMPs) that participate in the innate immune response and also have several pivotal roles in various biological processes. Such multifunctionality is commonly found among intrinsically disordered proteins. However, NK-lysins have never been systematically analyzed for intrinsic disorder. To fill this gap, the amino acid sequences of NK-lysins from various species were collected from UniProt and used for the comprehensive computational analysis to evaluate the propensity of these proteins for intrinsic disorder and to investigate the potential roles of disordered regions in NK-lysin functions. We analyzed abundance and peculiarities of intrinsic disorder distribution in all-known NK-lysins and showed that many NK-lysins are expected to have substantial levels of intrinsic disorder. Curiously, high level of intrinsic disorder was also found even in two proteins with known 3D-strucutres (NK-lysin from pig and human granulysin). Many of the identified disordered regions can be involved in protein-protein interactions. In fact, NK-lysins are shown to contain three to eight molecular recognition features; i.e. short structure-prone segments which are located within the long disordered regions and have a potential to undergo a disorder-to-order transition upon binding to a partner. Furthermore, these disordered regions are expected to have several sites of various posttranslational modifications. Our study shows that NK-lysins, which are AMPs with a set of prominent roles in the innate immune response, are expected to abundantly possess intrinsically disordered regions that might be related to multifunctionality of these proteins in the signal transduction pathways controlling the host response to pathogenic agents.
Journal Article England
The following values have no corresponding Zotero field: auth-address: a Faculty of Science, Department of Biological Sciences , University of Jeddah , Jeddah , Saudi Arabia. b Department of Cell Biology, Genetic Engineering and Biotechnology Division , National Research Centre , P.O. Box 12622, Gizza , Egypt. a Faculty of Science, Department of Biological Sciences , University of Jeddah , Jeddah , Saudi Arabia. b Department of Cell Biology, Genetic Engineering and Biotechnology Division , National Research Centre , P.O. Box 12622, Gizza , Egypt. c Faculty of Sciences, Department of Biological Sciences , King Abdulaziz University , P.O. Box 80203, Jeddah , Saudi Arabia. d Laboratory of Structural Dynamics, Stability and Folding of Proteins , Institute of Cytology, Russian Academy of Sciences , St. Petersburg , Russia. e Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine , University of South Florida , Tampa , FL , USA. alt-title: Journal of biomolecular structure & dynamics number: 4 accession-num: 26957115
Keywords: *Algorithms; Amino Acid Sequence; Animals; Anti-Infective Agents/*chemistry/metabolism; Antigens, Differentiation, T-Lymphocyte/*chemistry/metabolism; Computational Biology; Humans; Models, Molecular; Multigene Family; Protein Conformation; Proteolipids/*chemistry/metabolism; Sequence Homology, Amino Acid; Swine

Total chemical synthesis of a thermostable enzyme capable of polymerase chain reaction - Xu, W.; Jiang, W.; Wang, J.; Yu, L.; Chen, J.; Liu, X.; Liu, L.; Zhu, T. F. (Cell Discov., 2017)
Polymerase chain reaction (PCR) has been a defining tool in modern biology. Towards realizing mirror-image PCR, we have designed and chemically synthesized a mutant version of the 352-residue thermostable Sulfolobus solfataricus P2 DNA polymerase IV with l-amino acids and tested its PCR activity biochemically. To the best of our knowledge, this enzyme is the largest chemically synthesized protein reported to date. We show that with optimization of PCR conditions, the fully synthetic polymerase is capable of amplifying template sequences of up to 1.5 kb. The establishment of this synthetic route for chemically synthesizing DNA polymerase IV is a stepping stone towards building a d-enzyme system for mirror-image PCR, which may open up an avenue for the creation of many mirror-image molecular tools such as mirror-image systematic evolution of ligands by exponential enrichment.
The following values have no corresponding Zotero field: auth-address: School of Life Sciences, Tsinghua-Peking Joint Center for Life Sciences, Center for Synthetic and Systems Biology, Ministry of Education Key Laboratory of Bioinformatics, Tsinghua University, Beijing, China; Department of Chemistry, Tsinghua-Peking Joint Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Tsinghua University, Beijing, China. School of Life Sciences, Tsinghua-Peking Joint Center for Life Sciences, Center for Synthetic and Systems Biology, Ministry of Education Key Laboratory of Bioinformatics, Tsinghua University , Beijing, China. Department of Chemistry, Tsinghua-Peking Joint Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Tsinghua University , Beijing, China. alt-title: Cell discovery edition: 2017/03/08 accession-num: 28265464
Xu, Weiliang Jiang, Wenjun Wang, Jiaxing Yu, Linping Chen, Ji Liu, Xianyu Liu, Lei Zhu, Ting F England Cell Discov. 2017 Feb 28;3:17008. doi: 10.1038/celldisc.2017.8. eCollection 2017.

Sulfation of the human cytomegalovirus protein UL22A enhances binding to the chemokine RANTES - Wang, X.; Sanchez, J.; Stone, M. J.; Payne, R. J. (Angew. Chem. Int. Ed., 2017)
UL22A is an 83 amino acid chemokine-binding protein produced by human cytomegalovirus that likely assists the virus in dampening the host antiviral response. We proposed that UL22A is sulfated on two tyrosine residues and tested this hypothesis through the chemical synthesis of a small library of differentially sulfated protein variants. The (sulfo)proteins were efficiently prepared using a novel beta-selenoleucine motif to facilitate one-pot ligation-deselenization chemistry. Tyrosine sulfation of UL22A proved critical for RANTES binding, with the doubly sulfated variant exhibiting an improvement in binding of 2.5 orders of magnitude compared to the unmodified protein.
The following values have no corresponding Zotero field: auth-address: School of Chemistry, The University of Sydney, Sydney, NSW, 2006, Australia. Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC, 3800, Australia. number: 29 edition: 2017/05/11 accession-num: 28488292
Wang, Xiaoyi Sanchez, Julie Stone, Martin J Payne, Richard J Germany International ed. in English Angew Chem Int Ed Engl. 2017 Jul 10;56(29):8490-8494. doi: 10.1002/anie.201703059. Epub 2017 May 23.

Labeling and single-molecule methods to monitor G protein-coupled receptor dynamics - Tian, He; Fürstenberg, Alexandre; Huber, Thomas (Chem. Rev., 2017)
The following values have no corresponding Zotero field: number: 1 publisher: American Chemical Society

General, mild, and metal-free synthesis of phenyl selenoesters from anhydrides and their use in peptide synthesis - Temperini, Andrea; Piazzolla, Francesca; Minuti, Lucio; Curini, Massimo; Siciliano, Carlo (J. Org. Chem., 2017)
doi: 10.1021/acs.joc.7b00173 0022-3263 doi: 10.1021/acs.joc.7b00173
The following values have no corresponding Zotero field: number: 9 publisher: American Chemical Society

Practical chemical synthesis of atypical ubiquitin chains by using an isopeptide-linked Ub isomer - Tang, Shan; Liang, Lu-Jun; Si, Yan-Yan; Gao, Shuai; Wang, Jia-Xing; Liang, Jun; Mei, Ziqing; Zheng, Ji-Shen; Liu, Lei (Angew. Chem. Int. Ed., 2017)
Chemical ubiquitination is an effective approach for accessing structurally defined, atypical ubiquitin (Ub) chains that are difficult to prepare by other techniques. Herein, we describe a strategy that uses a readily accessible premade isopeptide-linked 76-mer (isoUb), which has an N-terminal Cys and a C-terminal hydrazide, as the key building block to assemble atypical Ub chains in a modular fashion. This method avoids the use of auxiliary-modified Lys and instead employs the canonical and therefore more robust Cys-based native chemical ligation technique. The efficiency and capacity of this isoUb-based strategy is exemplified by the cost-effective synthesis of several linkage- and length-defined atypical Ub chains, including K27-linked tetra-Ub and K11/K48-branched tri-, tetra-, penta-, and hexa-Ubs.
The following values have no corresponding Zotero field: number: 43
Keywords: native chemical ligation; post-translational modifications; protein chemical synthesis; proteolysis; ubiquitin

One-pot four-segment ligation using seleno- and thioesters: Synthesis of superoxide dismutase - Takei, Toshiki; Andoh, Tomoshige; Takao, Toshifumi; Hojo, Hironobu (Angew. Chem. Int. Ed., 2017)
The synthesis of a peptide selenoester was efficiently carried out by the 9-fluorenylmethoxycarbonyl (Fmoc) method using N-alkylcysteine, at the C-terminus of the peptide, as the N-to-S acyl shift device. The selenoester selectively reacted with the terminal amino group of the peptide aryl thioester in the presence of N,N-diisopropylethylamine and dipyridyldisulfide, thus leaving the aryl thioester intact. Combined with silver-ion-promoted and silver-ion-free thioester activation methods, a one-pot four-segment ligation was realized. The method was successfully used to assemble the entire sequence of superoxide dismutase (SOD), which is composed of 153 amino-acid residues, in one pot. After the folding reaction, the fully active SOD was obtained.
The following values have no corresponding Zotero field: number: 49
Keywords: chemical ligation; peptides; selenium; silver; synthetic methods

A facile N-mercaptoethoxyglycinamide (MEGA) linker approach to peptide thioesterification and cyclization - Shelton, P. M.; Weller, C. E.; Chatterjee, C. (J. Am. Chem. Soc., 2017)
The C-terminal electrophilic activation of peptides by alpha-thioesterification requires strongly acidic conditions or complex chemical manipulations, which ultimately limit functional group compatibility and broad utility. Herein, we report a readily accessible N-mercaptoethoxyglycinamide (MEGA) solid-phase linker for the facile synthesis of latent peptide alpha-thioesters. Incubating peptide-MEGA sequences with 2-mercaptoethanesulfonic acid at mildly acidic pH yielded alpha-thioesters that were directly used in NCL without purification. The MEGA linker yielded robust access to thioesters ranging in length from 4 to 35 amino acids, and greatly simplified the synthesis of cyclic peptides. Finally, the high utility of MEGA was demonstrated by the one-pot synthesis of a functional analog of the Sunflower Trypsin Inhibitor 1.
Shelton, Patrick M M Weller, Caroline E Chatterjee, Champak R01 GM110430/GM/NIGMS NIH HHS/ J Am Chem Soc. 2017 Mar 22;139(11):3946-3949. doi: 10.1021/jacs.6b13271. Epub 2017 Mar 9.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, University of Washington , Seattle, Washington 98195, United States. alt-title: Journal of the American Chemical Society number: 11 edition: 2017/02/24 accession-num: 28230996

Direct beta-Selective Hydrocarboxylation of Styrenes with CO2 Enabled by Continuous Flow Photoredox Catalysis - Seo, H.; Liu, A.; Jamison, T. F. (J Am Chem Soc, 2017)
The direct beta-selective hydrocarboxylation of styrenes under atmospheric pressure of CO2 has been developed using photoredox catalysis in continuous flow. The scope of this methodology was demonstrated with a range of functionalized terminal styrenes, as well as alpha-substituted and beta-substituted styrenes.
Seo, Hyowon Liu, Aofei Jamison, Timothy F J Am Chem Soc. 2017 Oct 11;139(40):13969-13972. doi: 10.1021/jacs.7b05942. Epub 2017 Sep 27.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Massachusetts Institute of Technology , Cambridge, Massachusetts 02139, United States. alt-title: Journal of the American Chemical Society number: 40 edition: 2017/09/28 accession-num: 28953365

Photoredox activation of carbon dioxide for amino acid synthesis in continuous flow - Seo, H.; Katcher, M. H.; Jamison, T. F. (Nat Chem, 2017)
Although carbon dioxide (CO2) is highly abundant, its low reactivity has limited its use in chemical synthesis. In particular, methods for carbon-carbon bond formation generally rely on two-electron mechanisms for CO2 activation and require highly activated reaction partners. Alternatively, radical pathways accessed via photoredox catalysis could provide new reactivity under milder conditions. Here we demonstrate the direct coupling of CO2 and amines via the single-electron reduction of CO2 for the photoredox-catalysed continuous flow synthesis of alpha-amino acids. By leveraging the advantages of utilizing gases and photochemistry in flow, a commercially available organic photoredox catalyst effects the selective alpha-carboxylation of amines that bear various functional groups and heterocycles. The preliminary mechanistic studies support CO2 activation and carbon-carbon bond formation via single-electron pathways, and we expect that this strategy will inspire new perspectives on using this feedstock chemical in organic synthesis.
Seo, Hyowon Katcher, Matthew H Jamison, Timothy F F32 GM108181/GM/NIGMS NIH HHS/ England Nat Chem. 2017 May;9(5):453-456. doi: 10.1038/nchem.2690. Epub 2016 Dec 26.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. alt-title: Nature chemistry number: 5 edition: 2017/04/22 accession-num: 28430203

Atom efficient preparation of zinc selenates for the synthesis of selenol esters under "on water" conditions - Sancineto, Luca; Pinto Vargas, Jaqueline; Monti, Bonifacio; Arca, Massimiliano; Lippolis, Vito; Perin, Gelson; Lenardao, Eder; Santi, Claudio (Molecules, 2017)
The following values have no corresponding Zotero field: number: 6 accession-num: doi:10.3390/molecules22060953

1,2,4-Triazole-aided native chemical ligation between peptide-N-acyl-N'-methyl-benzimidazolinone and cysteinyl peptide - Sakamoto, Ken; Tsuda, Shugo; Nishio, Hideki; Yoshiya, Taku (Chem. Commun., 2017)
1,2,4-Triazole facilitated native chemical ligation (NCL) between peptide-MeNbz (MeNbz: N-acyl-N[prime or minute]-methyl-benzimidazolinone) and a cysteinyl peptide in the absence of thiol additives. The method enabled one-pot desulfurization and iodine oxidation after NCL. Additionally, the direct isolation of the target peptide from the NCL reaction mixture with an activated thiopropyl-Sepharose resin was achieved.
The following values have no corresponding Zotero field: number: 90 publisher: The Royal Society of Chemistry work-type: 10.1039/C7CC07817J

Peptide Weinreb amide derivatives as thioester precursors for native chemical ligation - Rao, C.; Liu, C. F. (Org. Biomol. Chem., 2017)
Peptide Weinreb amide derivatives with an N-substituted mercaptoethyl group are designed as thioester precursors for native chemical ligation. We show that these amides undergo rapid ligation with a cysteinyl peptide under normal NCL conditions to form various Xaa-Cys peptide bonds, including the difficult Val-Cys junction. Facile synthesis of the Weinreb amide linkers allows easy access to this new type of peptide thioester precursor by standard Fmoc solid phase synthesis.
Rao, Chang Liu, Chuan-Fa England Org Biomol Chem. 2017 Mar 28;15(12):2491-2496. doi: 10.1039/c7ob00103g. Epub 2017 Feb 7.
The following values have no corresponding Zotero field: auth-address: School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551. cfliu@ntu.edu.sg. alt-title: Organic & biomolecular chemistry number: 12 edition: 2017/02/09 accession-num: 28170021

Synthesis of proteins by native chemical ligation-desulfurization strategies - Premdjee, B.; Payne, R. J. (Chemical Ligation. Tools for Biomolecule Synthesis and Modification, 2017)
Keywords: #nosource

A thermostable D-polymerase for mirror-image PCR - Pech, A.; Achenbach, J.; Jahnz, M.; Schulzchen, S.; Jarosch, F.; Bordusa, F.; Klussmann, S. (Nucleic Acids Res., 2017)
Biological evolution resulted in a homochiral world in which nucleic acids consist exclusively of d-nucleotides and proteins made by ribosomal translation of l-amino acids. From the perspective of synthetic biology, however, particularly anabolic enzymes that could build the mirror-image counterparts of biological macromolecules such as l-DNA or l-RNA are lacking. Based on a convergent synthesis strategy, we have chemically produced and characterized a thermostable mirror-image polymerase that efficiently replicates and amplifies mirror-image (l)-DNA. This artificial enzyme, dubbed d-Dpo4-3C, is a mutant of Sulfolobus solfataricus DNA polymerase IV consisting of 352 d-amino acids. d-Dpo4-3C was reliably deployed in classical polymerase chain reactions (PCR) and it was used to assemble a first mirror-image gene coding for the protein Sso7d. We believe that this d-polymerase provides a valuable tool to further investigate the mysteries of biological (homo)chirality and to pave the way for potential novel life forms running on a mirror-image genome.
Pech, Andreas Achenbach, John Jahnz, Michael Schulzchen, Simone Jarosch, Florian Bordusa, Frank Klussmann, Sven England Nucleic Acids Res. 2017 Apr 20;45(7):3997-4005. doi: 10.1093/nar/gkx079.
The following values have no corresponding Zotero field: auth-address: NOXXON Pharma AG, Weinbergweg 23, 06120 Halle (Saale), Germany. NOXXON Pharma AG, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany. Institute of Biochemistry and Biotechnology, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Strasse 3, 06120 Halle (Saale), Germany. alt-title: Nucleic acids research number: 7 edition: 2017/02/06 accession-num: 28158820
Keywords: Archaeal Proteins/genetics; DNA Polymerase beta/chemical synthesis/*genetics/metabolism; DNA-Binding Proteins/genetics; DNA/*biosynthesis/chemistry; Enzyme Stability; Mutation; Stereoisomerism; Sulfolobus solfataricus/enzymology; Temperature

Total synthesis of O-GalNacylated antifreeze glycoprotein using the switchable reactivity of peptidyl-N-pivaloylguanidine - Orii, R.; Sakamoto, N.; Fukami, D.; Tsuda, S.; Izumi, M.; Kajihara, Y.; Okamoto, R. (Chem. Eur. J., 2017)
Antifreeze glycoprotein (AFGP) is an O-glycoprotein that displays antifreeze activity through depression of the freezing point of water. GalNAc is a core sugar structure of AFGP, and contributes to induce antifreeze activity of this glycoprotein. However, the general functional role that this sugar plays at the molecular level is still unknown. To elucidate this, it is essential to determine the relationship between structure and activity of O-GalNAcylated AFGP using homogeneous glycoproteins. Thus, the total synthesis of homogeneous O-GalNAcylated AFGP was conducted by using a unique peptide derivative: peptidyl-N-pivaloylguanidine. It was found that peptidyl-N-pivaloylguanidine is an "unreactive" peptide in peptide coupling reactions but is interconvertible with a "reactive" peptide-alpha-thioester by means of a simple treatment under buffer condition at pH=7 to 8. The unique switchable reactivity of peptidyl-N-pivaloylguanidine enabled an efficient sequential peptide coupling strategy. By using this strategy, various lengths of homogeneous O-GalNAcylated AFGP were synthesized, including one that was 120 amino acids in length, with 40 O-GalNAcylation sites. The structural analysis by circular dichroism spectroscopy and evaluation of the antifreeze activity of the synthetic AFGP(GalNAc)s revealed that the simple O-glycosylation with GalNAc is essential for both structural and functional basis of AFGP to exhibit antifreeze activity.
Orii, Ryo Sakamoto, Noriko Fukami, Daichi Tsuda, Sakae Izumi, Masayuki Kajihara, Yasuhiro Okamoto, Ryo Germany Weinheim an der Bergstrasse, Germany Chemistry. 2017 Jul 12;23(39):9253-9257. doi: 10.1002/chem.201702243. Epub 2017 Jun 27.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Graduate School of Science, Osaka University, 1-1, Toyonaka, Osaka, 5600043, Japan. Transdisciplinary Life Science Course, Graduate School of Life Science, Hokkaido University and Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 2-17-2-1 Tsukisamu-Higashi, Toyohira, Sapporo, Hokkaido, 0628517, Japan. number: 39 edition: 2017/05/19 accession-num: 28516497

A simple and traceless solid phase method simplifies the assembly of large peptides and the access to challenging proteins - Ollivier, N.; Desmet, R.; Drobecq, H.; Blanpain, A.; Boll, E.; Leclercq, B.; Mougel, A.; Vicogne, J.; Melnyk, O. (Chem. Sci., 2017)
Chemical protein synthesis gives access to well-defined native or modified proteins that are useful for studying protein structure and function. The majority of proteins synthesized up to now have been produced using native chemical ligation (NCL) in solution. Although there are significant advantages to assembling large peptides or proteins by solid phase ligation, reports of such approaches are rare. We report a novel solid phase method for protein synthesis which relies on the chemistry of the acetoacetyl group and ketoxime ligation for the attachment of the peptide to the solid support, and on a tandem transoximation/rearrangement process for the detachment of the target protein. Importantly, we show that the combination of solid phase and solution ligation techniques facilitates the production of a challenging and biologically active protein made of 180 amino acids. We show also that the solid phase method enables the purification of complex peptide segments through a chemoselective solid phase capture/release approach.
2041-6520 10.1039/C7SC01912B
Cited By :1
Cited By :1
Cited By :1
Export Date: 25 May 2018

The n→π* interaction - Newberry, Robert W.; Raines, Ronald T. (Acc. Chem. Res., 2017)
The following values have no corresponding Zotero field: number: 8 publisher: American Chemical Society

Synthesis and Utilization of Nitroalkyne Equivalents in Batch and Continuous Flow - Morse, P. D.; Jamison, T. F. (Angew Chem Int Ed Engl, 2017)
We report a method for overcoming the low stability of nitroalkynes through the development of nitrated vinyl silyltriflate equivalents. Because of their instability, nitroalkynes have only rarely been utilized in synthesis. The reactivity of these silyltriflates, which are prepared in situ, is exemplified by dipolar cycloaddition reactions with nitrones to give highly substituted 4-nitro-4-isoxazolines in high yields. This approach has proven general for several different alkyl and aryl substituted alkynes. In order to minimize the accumulation of potentially hazardous reaction intermediates, we have also developed a continuous flow variant of this method that is capable of carrying out the entire reaction sequence in a good yield and a short residence time.
Morse, Peter D Jamison, Timothy F Germany International ed. in English Angew Chem Int Ed Engl. 2017 Nov 6;56(45):13999-14002. doi: 10.1002/anie.201706157. Epub 2017 Oct 4.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA, 02139, USA. number: 45 edition: 2017/09/21 accession-num: 28929565

Accelerated protein synthesis via one-pot ligation-deselenization chemistry - Mitchell, Nicholas J.; Sayers, Jessica; Kulkarni, Sameer S.; Clayton, Daniel; Goldys, Anna M.; Ripoll-Rozada, Jorge; Barbosa Pereira, Pedro José; Chan, Bun; Radom, Leo; Payne, Richard J. (Chem., 2017)
Summary Peptide ligation chemistry has revolutionized protein science by facilitating access to synthetic proteins. Here, we describe the development of additive-free ligation-deselenization chemistry at β-selenoaspartate and γ-selenoglutamate that enables the generation of native polypeptide products on unprecedented timescales. The deselenization step is chemoselective in the presence of unprotected selenocysteine, which is highlighted in the synthesis of selenoprotein K. The power of the methodology is also showcased through the synthesis of three tick-derived thrombin-inhibiting proteins, each of which were assembled, purified, and isolated for biological assays within a few hours. The methodology described here should serve as a powerful means of accessing synthetic proteins, including therapeutic leads, in the future.
The following values have no corresponding Zotero field: number: 5
Keywords: peptide synthesis; selenium; proteins; quantum chemistry calculations; SDG3: Good health and well-being; SDG9: Industry, innovation, and infrastructure

Native chemical ligation directed by photocleavable peptide nucleic acid (PNA) templates - Middel, Stephen; Panse, Cornelia H.; Nawratil, Swantje; Diederichsen, Ulf (ChemBioChem, 2017)
A novel peptide–peptide ligation strategy is introduced that has the potential to provide peptide libraries of linearly or branched coupled fragments and will be suited to introduce simultaneous protein modifications at different ligation sites. Ligation is assisted by templating peptide nucleic acid (PNA) strands, and therefore, ligation specificity is solely encoded by the PNA sequence. PNA templating, in general, allows for various kinds of covalent ligation reactions. As a proof of principle, a native chemical ligation strategy was elaborated. This PNA-templated ligation includes easy on-resin procedures to couple linkers and PNA to the respective peptides, and a traceless photocleavage of the linker/PNA oligomer after the ligation step. A 4,5-dimethoxy-2-nitrobenzaldehyde-based linker that allowed the photocleavable linkage of two bio-oligomers was developed.
The following values have no corresponding Zotero field: number: 23
Keywords: native chemical ligation; peptides; peptide nucleic acids; photochemistry; template synthesis

Protein chemical synthesis by SEA ligation - Melnyk, O.; Vicogne, J.; Simonneau, C. (Chemical Ligation. Tools for Biomolecule Synthesis and Modification, 2017)
Keywords: #nosource

Towards More Efficient, Greener Syntheses through Flow Chemistry - Lummiss, J. A. M.; Morse, P. D.; Beingessner, R. L.; Jamison, T. F. (Chem Rec, 2017)
Technological advances have an important role in the design of greener synthetic processes. In this Personal Account, we describe a wide range of thermal, photochemical, catalytic, and biphasic chemical transformations examined by our group. Each of these demonstrate how the merits of a continuous flow synthesis platform can align with some of the goals put forth by the Twelve Principles of Green Chemistry. In particular, we illustrate the potential for improved reaction efficiency in terms of atom economy, product yield and reaction rates, the ability to design synthetic process with chemical and solvent waste reduction in mind as well as highlight the benefits of the real-time monitoring capabilities in flow for highly controlled synthetic output.
Lummiss, Justin A M Morse, Peter D Beingessner, Rachel L Jamison, Timothy F New York, N.Y. Chem Rec. 2017 Jul;17(7):667-680. doi: 10.1002/tcr.201600139. Epub 2017 Feb 28.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA. number: 7 edition: 2017/03/01 accession-num: 28245339 work-type: Review Research Support, Non-U.S. Gov't

A Rapid Total Synthesis of Ciprofloxacin Hydrochloride in Continuous Flow - Lin, H.; Dai, C.; Jamison, T. F.; Jensen, K. F. (Angew. Chem. Int. Ed., 2017)
Within a total residence time of 9 min, the sodium salt of ciprofloxacin was prepared from simple building blocks via a linear sequence of six chemical reactions in five flow reactors. Sequential offline acidifications and filtrations afforded ciprofloxacin and ciprofloxacin hydrochloride. The overall yield of the eight-step sequence was 60 %. No separation of intermediates was required throughout the synthesis when a single acylation reaction was applied to remove the main byproduct, dimethylamine.
Lin, Hongkun Dai, Chunhui Jamison, Timothy F Jensen, Klavs F Germany International ed. in English Angew Chem Int Ed Engl. 2017 Jul 17;56(30):8870-8873. doi: 10.1002/anie.201703812. Epub 2017 Jun 20.
The following values have no corresponding Zotero field: auth-address: Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA. Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA. number: 30 edition: 2017/06/01 accession-num: 28561939

Removable backbone modification method for the chemical synthesis of membrane proteins - Li, Jia-Bin; Tang, Shan; Zheng, Ji-Shen; Tian, Chang-Lin; Liu, Lei (Acc. Chem. Res., 2017)
The following values have no corresponding Zotero field: number: 5 publisher: American Chemical Society

Recent advances in the preparation of Fmoc-SPPS-based peptide thioester and its surrogates for NCL-type reactions - Li, Hongxing; Dong, Suwei (Sci. China Chem., 2017)
Solid phase peptide synthesis (SPPS) based on Fmoc chemistry has become a commonly used technique in peptide chemistry, as it can be easily conducted using automated machine, and not requiring highly toxic HF in comparison to Boc-SPPS. With the fast development in the emerging field of protein chemical synthesis, many efforts have been endeavored aiming to find more efficient methods for preparing peptide fragments required in ligation reactions. This review briefly summarizes recent advances in the engineering and modification of Fmoc-SPPS-derived peptides, which can be used as the N-terminal fragments in a native chemical ligation (NCL) or NCL-type ligation reactions.
The following values have no corresponding Zotero field: number: 2 label: Li2017 work-type: journal article

Aligator: A computational tool for optimizing total chemical synthesis of large proteins - Jacobsen, M. T.; Erickson, P. W.; Kay, M. S. (Bioorg. Med. Chem., 2017)
The scope of chemical protein synthesis (CPS) continues to expand, driven primarily by advances in chemical ligation tools (e.g., reversible solubilizing groups and novel ligation chemistries). However, the design of an optimal synthesis route can be an arduous and fickle task due to the large number of theoretically possible, and in many cases problematic, synthetic strategies. In this perspective, we highlight recent CPS tool advances and then introduce a new and easy-to-use program, Aligator (Automated Ligator), for analyzing and designing the most efficient strategies for constructing large targets using CPS. As a model set, we selected the E. coli ribosomal proteins and associated factors for computational analysis. Aligator systematically scores and ranks all feasible synthetic strategies for a particular CPS target. The Aligator script methodically evaluates potential peptide segments for a target using a scoring function that includes solubility, ligation site quality, segment lengths, and number of ligations to provide a ranked list of potential synthetic strategies. We demonstrate the utility of Aligator by analyzing three recent CPS projects from our lab: TNFalpha (157 aa), GroES (97 aa), and DapA (312 aa). As the limits of CPS are extended, we expect that computational tools will play an increasingly important role in the efficient execution of ambitious CPS projects such as production of a mirror-image ribosome.
Jacobsen, Michael T Erickson, Patrick W Kay, Michael S England Bioorg Med Chem. 2017 Sep 15;25(18):4946-4952. doi: 10.1016/j.bmc.2017.05.061. Epub 2017 Jun 3.
The following values have no corresponding Zotero field: auth-address: Department of Biochemistry, University of Utah School of Medicine, 15 North Medical Drive East, Room 4100, Salt Lake City, UT 84112-5650, United States. Department of Biochemistry, University of Utah School of Medicine, 15 North Medical Drive East, Room 4100, Salt Lake City, UT 84112-5650, United States. Electronic address: kay@biochem.utah.edu. alt-title: Bioorganic & medicinal chemistry number: 18 edition: 2017/06/28 accession-num: 28651912 work-type: Review
Keywords: *Software; Chaperonin 10/chemical synthesis/chemistry; Chaperonin 60/chemical synthesis/chemistry; Computational Biology/*methods; Escherichia coli/metabolism; Proteins/*chemical synthesis/chemistry; Ribosomal Proteins/chemical synthesis/chemistry; Tumor Necrosis Factor-alpha/chemical synthesis/chemistry

Solid-phase synthesis of peptide selenoesters via a side-chain anchoring strategy - Hanna, Cameron C.; Kulkarni, Sameer S.; Watson, Emma E.; Premdjee, Bhavesh; Payne, Richard J. (Chem. Commun., 2017)
Peptide selenoesters have recently emerged as key building blocks for the ligation-based assembly of large polypeptides and proteins. Herein, we report an efficient solid-phase method for the high yielding and epimerisation-free synthesis of peptide selenoesters using a side-chain immobilisation strategy.
The following values have no corresponding Zotero field: number: 39 publisher: The Royal Society of Chemistry work-type: 10.1039/C7CC00823F

Controlling the supramolecular assembly of nucleosomes asymmetrically modified on H4 - Guidotti, Nora; Lechner, Carolin C.; Fierz, Beat (Chem. Commun., 2017)
In stem cells, H4 proteins carrying different modifications coexist within single nucleosomes. For functional studies, we report the synthesis of such asymmetric nucleosomes. Asymmetry is achieved by transiently crosslinking H4 by a traceless, protease-removable tag introduced via an isopeptide linkage. These nucleosomes are used to study Set8 activity, a key methyltransferase.
1359-7345 10.1039/C7CC06180C
The following values have no corresponding Zotero field: publisher: The Royal Society of Chemistry

Serine promoted synthesis of peptide thioester-precursor on solid support for native chemical ligation - Elashal, H. E.; Sim, Y. E.; Raj, M. (Chem. Sci., 2017)
Fmoc solid phase peptide synthesis of thioesters for the chemical synthesis of proteins via native chemical ligation is a challenge. We have developed a versatile approach for direct synthesis of peptide thioesters from a solid support utilizing Fmoc chemistry. Peptide thioester synthesis is performed by the formation of a cyclic urethane moiety via a selective reaction of the backbone amide chain with the side group of serine. The activated cyclic urethane moiety undergoes displacement by a thiol to generate the thioester directly from the solid support. Importantly, the method activates the serine residue for the synthesis of peptide thioesters; thus it is fully automated and free of the types of resins, linkers, handles, and unnatural amino acids typically needed for the synthesis of peptide thioesters using Fmoc chemistry. The resulting thioester is free of epimerization and is successfully applied for the synthesis of longer peptides using NCL.
Elashal, Hader E Sim, Yonnette E Raj, Monika England Chem Sci. 2017 Jan 1;8(1):117-123. doi: 10.1039/c6sc02162j. Epub 2016 Aug 16.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry , Seton Hall University , 400 South Orange Ave , South Orange , NJ 07079 , USA . Email: monika.raj@shu.edu. alt-title: Chemical science number: 1 edition: 2017/04/30 accession-num: 28451155

Accessing human selenoproteins through chemical protein synthesis - Dery, L.; Reddy, P. Sai; Dery, S.; Mousa, R.; Ktorza, O.; Talhami, A.; Metanis, N. (Chem. Sci., 2017)
The human body contains 25 selenoproteins, which contain in their sequence the twenty-first encoded amino acid, selenocysteine. About a dozen of these proteins remain functionally uncharacterized or poorly studied. Challenges in accessing these selenoproteins using traditional recombinant expressions have prevented biological characterization thus far. Chemical protein synthesis has the potential to overcome these hurdles. Here we report the first total chemical syntheses of two human selenoproteins, selenoprotein M (SELM) and selenoprotein W (SELW). The synthesis of the more challenging protein SELM was enabled using recent advances in the field of selenocysteine chemistry. This approach allows the preparation of selenoproteins in milligram quantities and in homogenous form, which should open new horizons for future studies to pursue a fuller biological understanding of their role in health and disease.
The following values have no corresponding Zotero field: number: 3 publisher: The Royal Society of Chemistry work-type: 10.1039/C6SC04123J

Chemical ligation. Tools for biomolecule synthesis and modification - D'Andrea, L. D.; Romanelli, A. (John Wiley & Sons, Inc., 2017)
Keywords: #nosource

A Unified Continuous Flow Assembly-Line Synthesis of Highly Substituted Pyrazoles and Pyrazolines - Britton, J.; Jamison, T. F. (Angew Chem Int Ed Engl, 2017)
A rapid and modular continuous flow synthesis of highly functionalized fluorinated pyrazoles and pyrazolines has been developed. Flowing fluorinated amines through sequential reactor coils mediates diazoalkane formation and [3+2] cycloaddition to generate more than 30 azoles in a telescoped fashion. Pyrazole cores are then sequentially modified through additional reactor modules performing N-alkylation and arylation, deprotection, and amidation to install broad molecular diversity in short order. Continuous flow synthesis enables the safe handling of diazoalkanes at elevated temperatures, and the use of aryl alkyne dipolarphiles under catalyst-free conditions. This assembly-line synthesis provides a flexible approach for the synthesis of agrochemicals and pharmaceuticals, as demonstrated by a four-step, telescoped synthesis of measles therapeutic, AS-136A, in a total residence time of 31.7 min (1.76 g h(-1) ).
Britton, Joshua Jamison, Timothy F Germany International ed. in English Angew Chem Int Ed Engl. 2017 Jul 17;56(30):8823-8827. doi: 10.1002/anie.201704529. Epub 2017 Jun 20.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA, 02139, USA. number: 30 edition: 2017/05/26 accession-num: 28544160

The assembly and use of continuous flow systems for chemical synthesis - Britton, J.; Jamison, T. F. (Nat Protoc, 2017)
The adoption of and opportunities in continuous flow synthesis ('flow chemistry') have increased significantly over the past several years. Continuous flow systems provide improved reaction safety and accelerated reaction kinetics, and have synthesised several active pharmaceutical ingredients in automated reconfigurable systems. Although continuous flow platforms are commercially available, systems constructed 'in-lab' provide researchers with a flexible, versatile, and cost-effective alternative. Herein, we describe the assembly and use of a modular continuous flow apparatus from readily available and affordable parts in as little as 30 min. Once assembled, the synthesis of a sulfonamide by reacting 4-chlorobenzenesulfonyl chloride with dibenzylamine in a single reactor coil with an in-line quench is presented. This example reaction offers the opportunity to learn several important skills including reactor construction, charging of a back-pressure regulator, assembly of stainless-steel syringes, assembly of a continuous flow system with multiple junctions, and yield determination. From our extensive experience of single-step and multistep continuous flow synthesis, we also describe solutions to commonly encountered technical problems such as precipitation of solids ('clogging') and reactor failure. Following this protocol, a nonspecialist can assemble a continuous flow system from reactor coils, syringes, pumps, in-line liquid-liquid separators, drying columns, back-pressure regulators, static mixers, and packed-bed reactors.
Britton, Joshua Jamison, Timothy F England Nat Protoc. 2017 Nov;12(11):2423-2446. doi: 10.1038/nprot.2017.102. Epub 2017 Oct 26.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. alt-title: Nature protocols number: 11 edition: 2017/10/27 accession-num: 29072707
Keywords: Benzylamines/chemistry; Chemistry Techniques, Synthetic/*instrumentation/methods; Chlorobenzenes/chemistry; Kinetics; Rheology/*instrumentation/methods; Sulfonamides/*chemical synthesis

In situ reconstitution of the adenosine A2A receptor in spontaneously formed synthetic liposomes - Brea, Roberto J.; Cole, Christian M.; Lyda, Brent R.; Ye, Libin; Prosser, R. Scott; Sunahara, Roger K.; Devaraj, Neal K. (J. Am. Chem. Soc., 2017)
doi: 10.1021/jacs.6b12830 0002-7863 doi: 10.1021/jacs.6b12830
The following values have no corresponding Zotero field: publisher: American Chemical Society

Minimizing E-factor in the continuous-flow synthesis of diazepam and atropine - Bedard, A. C.; Longstreet, A. R.; Britton, J.; Wang, Y.; Moriguchi, H.; Hicklin, R. W.; Green, W. H.; Jamison, T. F. (Bioorg Med Chem, 2017)
Minimizing the waste stream associated with the synthesis of active pharmaceutical ingredients (APIs) and commodity chemicals is of high interest within the chemical industry from an economic and environmental perspective. In exploring solutions to this area, we herein report a highly optimized and environmentally conscious continuous-flow synthesis of two APIs identified as essential medicines by the World Health Organization, namely diazepam and atropine. Notably, these approaches significantly reduced the E-factor of previously published routes through the combination of continuous-flow chemistry techniques, computational calculations and solvent minimization. The E-factor associated with the synthesis of atropine was reduced by 94-fold (about two orders of magnitude), from 2245 to 24, while the E-factor for the synthesis of diazepam was reduced by 4-fold, from 36 to 9.
Bedard, Anne-Catherine Longstreet, Ashley R Britton, Joshua Wang, Yuran Moriguchi, Hideki Hicklin, Robert W Green, William H Jamison, Timothy F England Bioorg Med Chem. 2017 Dec 1;25(23):6233-6241. doi: 10.1016/j.bmc.2017.02.002. Epub 2017 Feb 4.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Electronic address: tfj@mit.edu. alt-title: Bioorganic & medicinal chemistry number: 23 edition: 2017/03/13 accession-num: 28284869 work-type: Research Support, U.S. Gov't, Non-P.H.S. Research Support, Non-U.S. Gov't
Keywords: Atropine/chemical synthesis/*chemistry; Diazepam/chemical synthesis/*chemistry; Green Chemistry Technology; Hydrogen-Ion Concentration; Solvents/chemistry

Robust chemical synthesis of membrane proteins through a general method of removable backbone modification - Zheng, Ji-Shen; He, Yao; Zuo, Chao; Cai, Xiao-Ying; Tang, Shan; Wang, Zhipeng A.; Zhang, Long-Hua; Tian, Chang-Lin; Liu, Lei (J. Am. Chem. Soc., 2016)
The following values have no corresponding Zotero field: number: 10 publisher: American Chemical Society

One-pot N2C/C2C/N2N ligation to trap weak protein-protein interactions - Zhao, L.; Ehrt, C.; Koch, O.; Wu, Y. W. (Angew. Chem. Int. Ed., 2016)
Weak transient protein-protein interactions (PPIs) play an essential role in cellular dynamics. However, it is challenging to obtain weak protein complexes owing to their short lifetime. Herein we present a general and facile method for trapping weak PPIs in an unbiased manner using proximity-induced ligations. To expand the chemical ligation spectrum, we developed novel N2N (N-terminus to N-terminus) and C2C (C-terminus to C-terminus) ligation approaches. By using N2C (N-terminus to C-terminus), N2N, and C2C ligations in one pot, the interacting proteins were linked. The weak Ypt1:GDI interaction drove C2C ligation with t1/2 of 4.8 min and near quantitative conversion. The Ypt1-GDI conjugate revealed that binding of Ypt1 G-domain causes opening of the lipid-binding site of GDI, which can accommodate one prenyl group, giving insights into Rab membrane recycling. Moreover, we used this strategy to trap the KRas homodimer, which plays an important role in Ras signaling.
Journal Article Germany
The following values have no corresponding Zotero field: auth-address: Chemical Genomics Center of the Max Planck Society, Otto-Hahn-Strasse 15, 44227, Dortmund, Germany. TU Dortmund University, Faculty of Chemistry and Chemical Biology, Otto-Hahn-Strasse 6, 44227, Dortmund, Germany. TU Dortmund University, Faculty of Chemistry and Chemical Biology, Otto-Hahn-Strasse 6, 44227, Dortmund, Germany. Chemical Genomics Center of the Max Planck Society, Otto-Hahn-Strasse 15, 44227, Dortmund, Germany. yaowen.wu@mpi-dortmund.mpg.de. alt-title: Angewandte Chemie (International ed number: 28 accession-num: 27213482

Hybrid phase ligation for efficient synthesis of histone proteins - Yu, R. R.; Mahto, S. K.; Justus, K.; Alexander, M. M.; Howard, C. J.; Ottesen, J. J. (Org. Biomol. Chem., 2016)
We introduce a hybrid solid-solution phase ligation approach that combines the efficiency of solid phase ligation with solution phase ligation in the total synthesis of modified histone proteins. A two linker strategy allows analysis throughout work on the solid phase and maximizes yields through cleavage at an external Rink, while an internal HMBA linker allows the native carboxyl terminus for any protein sequence. We demonstrate this approach for two histone proteins: triple-acetylated H4-K5ac, K12ac, K91ac and CENP-A-K124ac.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry & Biochemistry, The Ohio State University, USA and Ohio State Biochemistry Program, The Ohio State University, Columbus, OH 43210, USA. ottesen.1@osu.edu. Department of Chemistry & Biochemistry, The Ohio State University, USA. alt-title: Organic & biomolecular chemistry number: 9 edition: 2016/01/30 accession-num: 26821702 work-type: Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.
Yu, Ruixuan R Mahto, Santosh K Justus, Kurt Alexander, Mallory M Howard, Cecil J Ottesen, Jennifer J R01 GM083055/GM/NIGMS NIH HHS/ GM083055/GM/NIGMS NIH HHS/ England Org Biomol Chem. 2016 Mar 7;14(9):2603-7. doi: 10.1039/c5ob02195b.
Keywords: Histones/*chemical synthesis/*chemistry; Molecular Conformation

Preparation of protein conjugates via homobifunctional diselenoester cross-linker - Yin, Xu-Guang; Gao, Xiao-Fei; Du, Jing-Jing; Zhang, Xiao-Kang; Chen, Xiang-Zhao; Wang, Jian; Xin, Ling-Ming; Lei, Ze; Liu, Zheng; Guo, Jun (Org. Lett., 2016)
Adipic acid diselenoester was developed as an efficient cross-linker for covalent protein conjugation with a variety of small molecular haptens, including mono- and disaccharides, peptide, fluorescence dye, and nicotine. Compared to the counterparts of N-hydroxysuccinimide (NHS) and p-nitrophenyl (PNP) linkers, the diselenoester linker demonstrates improved balance between reactivity and stability and coupling of haptens to proteins under mild conditions with high incorporation efficiency.
The following values have no corresponding Zotero field: number: 22 publisher: American Chemical Society

Selenocysteine as a latent bioorthogonal electrophilic probe for deubiquitylating enzymes - Whedon, S. D.; Markandeya, N.; Rana, A. S.; Weller, C. E.; Senger, N. A.; Turecek, F.; Strieter, E. R.; Chatterjee, C. (J Am Chem Soc, 2016)
Deubiquitylating enzymes (DUBs) remove ubiquitin (Ub) from various cellular proteins and render eukaryotic ubiquitylation a dynamic process. The misregulation of protein ubiquitylation is associated with many human diseases, and there is an urgent need to identify specific DUBs associated with therapeutically relevant targets of Ub. We report the development of two facile selenocysteine-based strategies to generate the DUB probe dehydroalanine (Dha). Optimized oxidative or alkylative elimination of Se yielded Dha at the C-terminus of Ub. The high utility of alkylative elimination, which is compatible with multiple thiols in Ub targets, was demonstrated by generating a probe derived from the Ub ligase, tripartite motif protein 25 (TRIM-25). Successful capture of the TRIM-25-associated DUB, ubiquitin specific protease 15, demonstrated the versa-tility of our chemical strategy toward identifying target-specific DUBs.
R01 GM110430/GM/NIGMS NIH HHS/United States Journal Article United States
The following values have no corresponding Zotero field: alt-title: Journal of the American Chemical Society accession-num: 27723317

Aromatic thiol-mediated cleavage of N-O bonds enables chemical ubiquitylation of folded proteins - Weller, C. E.; Dhall, A.; Ding, F.; Linares, E.; Whedon, S. D.; Senger, N. A.; Tyson, E. L.; Bagert, J. D.; Li, X.; Augusto, O.; Chatterjee, C. (Nat. Commun., 2016)
Access to protein substrates homogenously modified by ubiquitin (Ub) is critical for biophysical and biochemical investigations aimed at deconvoluting the myriad biological roles for Ub. Current chemical strategies for protein ubiquitylation, however, employ temporary ligation auxiliaries that are removed under harsh denaturing conditions and have limited applicability. We report an unprecedented aromatic thiol-mediated N-O bond cleavage and its application towards native chemical ubiquitylation with the ligation auxiliary 2-aminooxyethanethiol. Our interrogation of the reaction mechanism suggests a disulfide radical anion as the active species capable of cleaving the N-O bond. The successful semisynthesis of full-length histone H2B modified by the small ubiquitin-like modifier-3 (SUMO-3) protein further demonstrates the generalizability and compatibility of our strategy with folded proteins.
R01 GM110430/GM/NIGMS NIH HHS/United States Journal Article England
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, University of Washington, Seattle, Washington 98195, USA. Department of Chemistry, University of Washington, Seattle, Washington 98195, USA. Department of Chemistry, University of Washington, Seattle, Washington 98195, USA. Departamento de Bioquimica, Instituto de Quimica-Universidade de Sao Paulo, Sao Paulo 05513-970, Brazil. Department of Chemistry, University of Washington, Seattle, Washington 98195, USA. Department of Chemistry, University of Washington, Seattle, Washington 98195, USA. Department of Chemistry, University of Washington, Seattle, Washington 98195, USA. Department of Chemistry, Princeton University, Princeton, New Jersey 08544, USA. Department of Chemistry, University of Washington, Seattle, Washington 98195, USA. Departamento de Bioquimica, Instituto de Quimica-Universidade de Sao Paulo, Sao Paulo 05513-970, Brazil. Department of Chemistry, University of Washington, Seattle, Washington 98195, USA. alt-title: Nature communications accession-num: 27680493

Boc-SPPS: Compatible linker for the synthesis of peptide o-aminoanilides - Weidmann, Joachim; Dimitrijević, Elena; Hoheisel, Jörg D.; Dawson, Philip E. (Org. Lett., 2016)
A protection strategy is described for the efficient synthesis of peptide o-aminoanilides using in situ neutralization protocols for Boc-SPPS. On-resin protection of Boc-protected aminoacyl o-aminoanilides is achieved with 2-chlorobenzyl chloroformate. Activation through a peptidyl-benzotriazole intermediate allows for facile conversion to peptide-thioesters for use in native chemical ligation. In addition to providing a robust alternative to established thioester resins, as a latent thioester, the peptide o-aminoanilide has broad utility in convergent ligation strategies.
The following values have no corresponding Zotero field: number: 2 publisher: American Chemical Society

Antimicrobial properties of an immunomodulator - 15 kDa human granulysin - Wei, H. M.; Lin, L. C.; Wang, C. F.; Lee, Y. J.; Chen, Y. T.; Liao, Y. D. (PLoS One, 2016)
Granulysin, a cationic protein expressed by human natural killer cells and cytotoxic T lymphocytes, is a mediator for drug-induced Stevens-Johnson syndrome and graft-versus-host disease. Some 15 kDa granulysin are processed into 9 kDa forms and sequestered in cytolytic granules, while others are constitutively secreted into body fluids. Both 9 and 15 kDa granulysin have been shown to be a serum marker for cell-mediated immunity. Furthermore, 15 kDa is able to activate monocyte differentiation. However, its antimicrobial properties have not been clearly addressed. Here, we report a novel method to prepare both the soluble 9 and 15 kDa granulysin and show that the 15 kDa form is more effective than the 9 kDa form in exerting specific antimicrobial activity against Pseudomonas aeruginosa within a range of few micromolars. We also show that the 15 kDa granulysin is able to hyperpolarize the membrane potential and increase membrane permeability of treated bacteria. Interestingly, the bactericidal activity and membrane permeability of the granulysins were markedly reduced at lower pH (pH 5.4) as a result of probable increase in hydrophobicity of the granulysins. Additionally, we've also shown the granulysin to inhibit biofilm formation by P. aeruginosa. These results suggest that the 15 kDa granulysin exhibits a novel mechanism in bacteria killing in a way that's different from most antimicrobial peptides. Our novel granulysin preparation methodology will be useful for further study of action mechanisms of other antimicrobial, cytotoxic and immunomodulating properties in granulysin-mediated diseases.
Journal Article United States
The following values have no corresponding Zotero field: auth-address: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan. Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan. Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan. Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan. Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan. Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan. Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan. Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei, Taiwan. alt-title: PloS one number: 6 accession-num: 27276051
Keywords: Humans; Hydrogen-Ion Concentration; Anti-Infective Agents/chemistry/*pharmacology; Antigens, Differentiation, T-Lymphocyte/chemistry/*pharmacology; Biofilms/*drug effects/growth & development; Dose-Response Relationship, Drug; Immunologic Factors/chemistry/*pharmacology; Membrane Potentials/drug effects; Pseudomonas aeruginosa/*physiology

A synthetic molecular system capable of mirror-image genetic replication and transcription - Wang, Zimou; Xu, Weiliang; Liu, Lei; Zhu, Ting F. (Nat. Chem., 2016)
The following values have no corresponding Zotero field: publisher: Nature Publishing Group work-type: Article

C-terminal modification of fully unprotected peptide hydrazides via in situ generation of isocyanates - Vinogradov, Alexander A.; Simon, Mark D.; Pentelute, Bradley L. (Org. Lett., 2016)
The following values have no corresponding Zotero field: number: 6 publisher: American Chemical Society

N-sulfanylethylaminooxybutyramide (SEAoxy): A crypto-thioester compatible with Fmoc solid-phase peptide synthesis - Tsuda, S.; Mochizuki, M.; Sakamoto, K.; Denda, M.; Nishio, H.; Otaka, A.; Yoshiya, T. (Org. Lett., 2016)
An N-sulfanylethylaminooxybutyramide (SEAoxy) has been developed as a novel thioester equivalent for native chemical ligation. SEAoxy peptide was straightforwardly synthesized by conventional Fmoc solid-phase peptide synthesis without a problem. Moreover, SEAoxy peptide could be directly applied to native chemical ligation owing to the intramolecular N-to-S acyl shift that releases the peptide-thioester in situ. This methodology was successfully applied to the synthesis of two bioactive peptides.
Journal Article United States
The following values have no corresponding Zotero field: auth-address: Peptide Institute, Inc., Ibaraki, Osaka 567-0085, Japan. Peptide Institute, Inc., Ibaraki, Osaka 567-0085, Japan. Peptide Institute, Inc., Ibaraki, Osaka 567-0085, Japan. Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University , Tokushima 770-8505, Japan. Peptide Institute, Inc., Ibaraki, Osaka 567-0085, Japan. Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University , Tokushima 770-8505, Japan. Peptide Institute, Inc., Ibaraki, Osaka 567-0085, Japan. alt-title: Organic letters accession-num: 27805411

Development of a sufficiently reactive thioalkylester involving the side-chain thiol of cysteine applicable for kinetically controlled ligation - Tsuda, S.; Mochizuki, M.; Nishio, H.; Yoshiya, T.; Nishiuchi, Y. (Biopolymers, 2016)
N(alpha) -Trifluoroacetyl-Cys-Leu-NH2 (TfaC-Leu-NH2 ) was incorporated into thioesters through its side-chain thiol group to develop a more reactive peptide-thioester than the commonly used peptide-3-mercaptopropionic acid (MPA)-thioester. The TfaC-thioester could be readily synthesized by solid-phase peptide synthesis (SPPS) with Boc chemistry using in situ neutralization protocols in sufficient yield without any side reaction associated with the use of TfaC. This thioester proved to display a much higher reactivity in the thiol-free native chemical ligation (NCL) reaction than the MPA-thioester and to be comparable to the thioarylester, such as the 4-mercaptophenylacetic acid (MPAA)-thioester, in terms of the ligation rate. We were able to demonstrate the usefulness of the TfaC-thioester by using it to synthesize neuromedin S via a one-pot sequential NCL approach followed by desulfurization. (c) 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 503-511, 2016.
Journal Article United States
The following values have no corresponding Zotero field: auth-address: Peptide Institute, Inc., Ibaraki, Osaka, 567-0085, Japan. Peptide Institute, Inc., Ibaraki, Osaka, 567-0085, Japan. Peptide Institute, Inc., Ibaraki, Osaka, 567-0085, Japan. Graduate School of Science, Osaka University, Toyonaka, Osaka, 560-0043, Japan. Peptide Institute, Inc., Ibaraki, Osaka, 567-0085, Japan. Peptide Institute, Inc., Ibaraki, Osaka, 567-0085, Japan. alt-title: Biopolymers number: 4 accession-num: 26583564

Optimal peptide hydrazide ligation with C-terminus Asp, Asn, and Gln hydrazides - Tian, Xiaobo; Li, Jie; Huang, Wei (Tetrahedron Lett., 2016)
Peptide hydrazide ligation is a newly reported approach using C-terminus hydrazide as the precursor of thioester for ligation with N-terminus Cys-peptides. However, peptide hydrazides with C-terminus Asp, Asn, and Gln are difficult to generate because of cyclization side reaction happened during peptide cleavage from Wang resin. To prevent the cyclization, we chose the acid-sensitive CTC-resin as the support and utilized two-step cleavage strategy: (1) release the peptide hydrazide bearing side-chain protection from the support with 1% TFA; (2) remove the side-chain protection with 90% TFA to give the corresponding peptide hydrazides. Peptide ligation using these hydrazides with a Cys-peptide indicated the high efficiency in peptide elongation. The current study expands the scope of the peptide hydrazide ligation to all 20 natural amino acids at C-terminal.
The following values have no corresponding Zotero field: number: 38
Keywords: C-terminus cyclization; CTC-resin; Peptide hydrazide ligation

Theoretical calculation of pKa's of selenols in aqueous solution using an implicit solvation model and explicit water molecules - Thapa, Bishnu; Schlegel, H. Bernhard (J. Chem. Phys. A, 2016)
doi: 10.1021/acs.jpca.6b09520 1089-5639 doi: 10.1021/acs.jpca.6b09520
The following values have no corresponding Zotero field: number: 44 publisher: American Chemical Society

A straightforward method for automated Fmoc-based synthesis of bio-inspired peptide crypto-thioesters - Terrier, Victor P.; Adihou, Helene; Arnould, Mathieu; Delmas, Agnes F.; Aucagne, Vincent (Chem. Sci., 2016)
Despite recent advances, the direct Fmoc-based solid phase synthesis of peptide [small alpha]-thioesters for the convergent synthesis of proteins via native chemical ligation (NCL) remains a challenge in the field. We herein report a simple and general methodology, enabling access to peptide thioester surrogates. A novel C-terminal N-(2-hydroxybenzyl)cysteine thioesterification device based on an amide-to-thioester rearrangement was developed, and the resulting peptide crypto-thioesters can be directly used in NCL reactions with fast N [rightward arrow] S shift kinetics at neutral pH. These fast kinetics arise from our bio-inspired design, via intein-like intramolecular catalysis. Due to a well-positioned phenol moiety, an impressive >50 fold increase in the kinetic rate is observed compared to an O-methylated derivative. Importantly, the synthesis of this new device can be fully automated using inexpensive commercially available materials and does not require any post-synthetic steps prior to NCL. We successfully applied this new method to the synthesis of two long naturally-occurring cysteine-rich peptide sequences.
2041-6520 10.1039/C5SC02630J
The following values have no corresponding Zotero field: number: 1 publisher: The Royal Society of Chemistry

Thiol-mediated controlled ring-opening polymerization of cysteine-derived b-thiolactone and unique features of product polythioester - Suzuki, Masato; Makimura, Kazumasa; Matsuoka, Shin-ichi (Biomacromolecules, 2016)
doi: 10.1021/acs.biomac.5b01748 1525-7797 doi: 10.1021/acs.biomac.5b01748
The following values have no corresponding Zotero field: number: 3 publisher: American Chemical Society

Peptide conjugation to a polymer coating via native chemical ligation of azlactones for cell culture - Schmitt, S. K.; Trebatoski, D. J.; Krutty, J. D.; Xie, A. W.; Rollins, B.; Murphy, W. L.; Gopalan, P. (Biomacromolecules, 2016)
Conjugation of biomolecules for stable presentation is an essential step toward reliable chemically defined platforms for cell culture studies. In this work, we describe the formation of a stable and site-specific amide bond via the coupling of a cysteine terminated peptide at low concentration to an azlactone containing copolymer coating. A copolymer of polyethylene glycol methyl ether methacrylate-ran-vinyl azlactone-ran-glycidyl methacrylate P(PEGMEMA-r-VDM-r-GMA) was used to form a thin coating (20-30 nm) on silicon and polycarbonate substrates. The formation and stability of coating-peptide bonds for peptides containing free thiols and amines were quantified by X-ray photoelectron spectroscopy (XPS) after exposure to cell culture conditions. Peptides containing a thiol as the only nucleophile coupled via a thioester bond; however, the bond was labile under cell culture conditions and almost all the bound peptides were displaced from the surface over a period of 2 days. Coupling with N-terminal primary amine peptides resulted in the formation of an amide bond with low efficiency (<20%). In contrast, peptides containing an N-terminal cysteine, which contain both nucleophiles (free thiol and amine) in close proximity, bound with 67% efficiency under neutral pH, and were stable under the same conditions for 2 weeks. Control studies confirm that the stable amide formation was a result of an intramolecular rearrangement through a N-acyl intermediate that resembles native chemical ligation. Through a combination of XPS and cell culture studies, we show that the cysteine terminated peptides undergo a native chemical ligation process at low peptide concentration in aqueous media, short reaction time, and at room temperature resulting in the stable presentation of peptides beyond 2 weeks for cell culture studies.
Schmitt, Samantha K Trebatoski, David J Krutty, John D Xie, Angela W Rollins, Benjamin Murphy, William L Gopalan, Padma R01 GM050853/GM/NIGMS NIH HHS/ T32 GM008349/GM/NIGMS NIH HHS/ NIGMS 5 T32-GM08349/PHS HHS/ Biomacromolecules. 2016 Mar 14;17(3):1040-7. doi: 10.1021/acs.biomac.5b01682. Epub 2016 Feb 15.
The following values have no corresponding Zotero field: auth-address: Department of Materials Science and Engineering, double daggerDepartment of Biomedical Engineering, section signDepartment of Orthopedics and Rehabilitation, and parallelDepartment of Chemistry, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States. alt-title: Biomacromolecules number: 3 edition: 2016/02/03 accession-num: 26835552 work-type: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.
Keywords: Humans; Cell Line; Coated Materials, Biocompatible/*chemical synthesis/pharmacology; Cysteine/chemistry; Lactones/chemistry; Mesenchymal Stromal Cells/drug effects; Peptides/*chemistry; Polycarboxylate Cement/chemistry; Polyethylene Glycols/chemical synthesis/pharmacology; Polymethacrylic Acids/chemical synthesis/pharmacology; Silicones/chemistry

Imidazole-aided native chemical ligation: Imidazole as a one-pot desulfurization-amenable non-thiol-type alternative to 4-mercaptophenylacetic acid - Sakamoto, Ken; Tsuda, Shugo; Mochizuki, Masayoshi; Nohara, Yukie; Nishio, Hideki; Yoshiya, Taku (Chem. Eur. J., 2016)
Various bioactive proteins have been synthesized by native chemical ligation (NCL) and its combination with subsequent desulfurization (e.g., conversion from Cys to Ala). In NCL, excess 4-mercaptophenylacetic acid (MPAA) is generally added to facilitate the reaction. However, co-elution of MPAA with the ligation product during preparative high-performance liquid chromatography sometimes reduces its usefulness. In addition, contamination of MPAA disturbs subsequent desulfurization. Here, we report for the first time that imidazole can be adopted as an alternative to MPAA in NCL using a peptide-alkylthioester. The efficiency of the imidazole-aided NCL (Im-NCL) is similar to that of traditional MPAA-aided NCL. As model cases, we successfully synthesized adiponectin(19-107) and [Ser(PO3H2)65]-ubiquitin using Im-NCL with a one-pot desulfurization.
1521-3765
Keywords: native chemical ligation; chemical protein synthesis; desulfurization; imidazole; thiol additive free

Why Nature Chose Selenium - Reich, Hans J.; Hondal, Robert J. (ACS Chem. Biol., 2016)
doi: 10.1021/acschembio.6b00031 1554-8929 doi: 10.1021/acschembio.6b00031
The following values have no corresponding Zotero field: number: 4 publisher: American Chemical Society

HF-free Boc synthesis of peptide thioesters for ligation and cyclization - Raz, R.; Burlina, F.; Ismail, M.; Downward, J.; Li, J.; Smerdon, S. J.; Quibell, M.; White, P. D.; Offer, J. (Angew. Chem. Int. Ed., 2016)
We have developed a convenient method for the direct synthesis of peptide thioesters, versatile intermediates for peptide ligation and cyclic peptide synthesis. The technology uses a modified Boc SPPS strategy that avoids the use of anhydrous HF. Boc in situ neutralization protocols are used in combination with Merrifield hydroxymethyl resin and TFA/TMSBr cleavage. Avoiding HF extends the scope of Boc SPPS to post-translational modifications that are compatible with the milder cleavage conditions, demonstrated here with the synthesis of the phosphorylated protein CHK2. Peptide thioesters give easy, direct, access to cyclic peptides, illustrated by the synthesis of cyclorasin, a KRAS inhibitor.
Raz, Richard Burlina, Fabienne Ismail, Mohamed Downward, Julian Li, Jiejin Smerdon, Stephen J Quibell, Martin White, Peter D Offer, John MRC_MC_U117584228/Medical Research Council/United Kingdom Germany International ed. in English Angew Chem Int Ed Engl. 2016 Oct 10;55(42):13174-13179. doi: 10.1002/anie.201607657.
The following values have no corresponding Zotero field: auth-address: The Francis Crick Institute, 1 Midland road, London, NW1 1AT, UK. Sorbonne Universites, UPMC Univ Paris 06, ENS, CNRS, Laboratoire des Biomolecules (LBM), Paris, France. Departement de Chimie, ENS, PSL Research University, UPMC, Univ Paris 06, CNRS, LBM, Paris, France. Merck Chemicals, Padge Road, Beeston, Notts, NG9 2JR, UK. The Francis Crick Institute, 1 Midland road, London, NW1 1AT, UK. john.offer@francis.crick.ac.uk. number: 42 edition: 2016/09/23 accession-num: 27654901

Accelerating chemoselective peptide bond formation using bis(2-selenylethyl)amido peptide selenoester surrogates - Raibaut, Laurent; Cargoët, Marine; Ollivier, Nathalie; Chang, Yun Min; Drobecq, Herve; Boll, Emmanuelle; Desmet, Remi; Monbaliu, Jean-Christophe M.; Melnyk, Oleg (Chem. Sci., 2016)
Given the potential of peptide selenoesters for protein total synthesis and the paucity of methods for the synthesis of these sensitive peptide derivatives, we sought to explore the usefulness of the bis(2-selenylethyl)amido (SeEA) group, i.e. the selenium analog of the bis(2-sulfanylethyl)amido (SEA) group, for accelerating peptide bond formation. A chemoselective exchange process operating in water was devised for converting SEA peptides into the SeEA ones. Kinetic studies show that SeEA ligation, which relies on an initial N,Se-acyl shift process, proceeds significantly faster than SEA ligation. This property enabled the design of a kinetically controlled three peptide segment assembly process based on the sequential use of SeEA and SEA ligation reactions. The method was validated by the total synthesis of hepatocyte growth factor K1 (85 AA) and biotinylated NK1 (180 AA) domains.
2041-6520 10.1039/C5SC03459K
The following values have no corresponding Zotero field: publisher: The Royal Society of Chemistry

Hmb(off/on) as a switchable thiol protecting group for native chemical ligation - Qi, Y. K.; Tang, S.; Huang, Y. C.; Pan, M.; Zheng, J. S.; Liu, L. (Org. Biomol. Chem., 2016)
A new thiol protecting group Hmb(off/on) is described, which has a switchable activity that may be useful in the chemical synthesis of proteins. When placed on the side chain of Cys, Cys(Hmb(off)) is stable to trifluoroacetic acid (TFA) in the process of solid-phase peptide synthesis. When Cys(Hmb(off)) is treated with neutral aqueous buffers, it is cleanly converted to acid-labile Cys(Hmb(on)), which can later be fully deprotected by TFA to generate free Cys. The utility of Cys(Hmb(off/on)) is demonstrated by the chemical synthesis of an erythropoietin segment, EPO[Cys(98)-Arg(166)]-OH through native chemical ligation.
Journal Article England
The following values have no corresponding Zotero field: auth-address: Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China. lliu@mail.tsinghua.edu.cn and High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, China. jszheng@hmfl.cas.cn. Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China. lliu@mail.tsinghua.edu.cn. Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China. lliu@mail.tsinghua.edu.cn. Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China. lliu@mail.tsinghua.edu.cn. High Magnetic Field Laboratory, Chinese Academy of Sciences, Hefei 230031, China. jszheng@hmfl.cas.cn. Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, China. lliu@mail.tsinghua.edu.cn. alt-title: Organic & biomolecular chemistry number: 18 accession-num: 27102373

Insight into the SEA amide thioester equilibrium. Application to the synthesis of thioesters at neutral pH - Pira, S. L.; El Mahdi, O.; Raibaut, L.; Drobecq, H.; Dheur, J.; Boll, E.; Melnyk, O. (Org. Biomol. Chem., 2016)
The bis(2-sulfanylethyl)amide (SEA) N,S-acyl shift thioester surrogate has found a variety of useful applications in the field of protein total synthesis. Here we present novel insights into the SEA amide/thioester equilibrium in water which is an essential step in any reaction involving the thioester surrogate properties of the SEA group. We also show that the SEA amide thioester equilibrium can be efficiently displaced at neutral pH for accessing peptide alkylthioesters, i.e. the key components of the native chemical ligation (NCL) reaction.
Cited By :5
Cited By :5
Export Date: 25 May 2018
Export Date: 25 May 2018
Journal Article England

5-Methylisoxazole-3-carboxamide-directed palladium-catalyzed g-C(sp3)-H acetoxylation and application to the synthesis of g-mercapto amino acids for native chemical ligation - Pasunooti, Kalyan Kumar; Yang, Renliang; Banerjee, Biplab; Yap, Terence; Liu, Chuan-Fa (Org. Lett., 2016)
doi: 10.1021/acs.orglett.6b01160 1523-7060 doi: 10.1021/acs.orglett.6b01160
The following values have no corresponding Zotero field: number: 11 publisher: American Chemical Society

The road to the synthesis of "difficult peptides" - Paradis-Bas, Marta; Tulla-Puche, Judit; Albericio, Fernando (Chem. Soc. Rev., 2016)
The last decade has witnessed a renaissance of peptides as drugs. This progress, together with advances in the structural behavior of peptides, has attracted the interest of the pharmaceutical industry in these molecules as potential APIs. In the past, major peptide-based drugs were inspired by sequences extracted from natural structures of low molecular weight. In contrast, nowadays, the peptides being studied by academic and industrial groups comprise more sophisticated sequences. For instance, they consist of long amino acid chains and show a high tendency to form aggregates. Some researchers have claimed that preparing medium-sized proteins is now feasible with chemical ligation techniques, in contrast to medium-sized peptide syntheses. The complexity associated with the synthesis of certain peptides is exemplified by the so-called "difficult peptides", a concept introduced in the 80's. This refers to sequences that show inter- or intra-molecular [small beta]-sheet interactions significant enough to form aggregates during peptide synthesis. These structural associations are stabilized and mediated by non-covalent hydrogen bonds that arise on the backbone of the peptide and-depending on the sequence-are favored. The tendency of peptide chains to aggregate is translated into a list of common behavioral features attributed to "difficult peptides" which hinder their synthesis. In this regard, this manuscript summarizes the strategies used to overcome the inherent difficulties associated with the synthesis of known "difficult peptides". Here we evaluate several external factors, as well as methods to incorporate chemical modifications into sequences, in order to describe the strategies that are effective for the synthesis of "difficult peptides". These approaches have been classified and ordered to provide an extensive guide for achieving the synthesis of peptides with the aforementioned features.
The following values have no corresponding Zotero field: number: 3 publisher: The Royal Society of Chemistry work-type: 10.1039/C5CS00680E

Quasi-racemic X-ray structures of K27-linked ubiquitin chains prepared by total chemical synthesis - Pan, Man; Gao, Shuai; Zheng, Yong; Tan, Xiaodan; Lan, Huan; Tan, Xianglong; Sun, Demeng; Lu, Lining; Wang, Tian; Zheng, Qingyun; Huang, Yichao; Wang, Jiawei; et al. (J. Am. Chem. Soc., 2016)
The following values have no corresponding Zotero field: number: 23 publisher: American Chemical Society

An efficient solid-phase synthesis of peptidyl-N-acetylguanidines for use in native chemical ligation - Okamoto, R.; Isoe, M.; Izumi, M.; Kajihara, Y. (J. Pept. Sci., 2016)
In the modern protocols of chemical protein syntheses, peptide-alpha-thioesters have been used as key components for the assembly of full-length polypeptides through chemoselective peptide coupling reactions. A variety of thioester precursors have been developed for the synthesis of the peptide-alpha-thioesters by Fmoc solid phase peptide synthesis (Fmoc-SPPS). Recently our group found a peptidyl-N-acetylguanidine as a new peptide-alpha-thioester precursor. This peptide derivative can be converted into a corresponding peptide-alpha-thioester only by treatment with an excess amount of a thiol in aqueous buffers at around neutral pH. This unique property allowed us to envision the practical use of the peptidyl-N-acetylguanidines for the chemical syntheses of proteins; however, an efficient synthetic method has been lacking. Herein, we report an efficient solid-phase synthesis of peptidyl-N-acetylguanidines. This new synthetic method employing selective activation and cleavage of a peptide bond successfully provided peptidyl-N-acetylguanidines from the on-resin protected peptides prepared by standard Fmoc-SPPS. We also evaluated the reactivity of a peptidyl-N-acetylguanidine in native chemical ligation through the synthesis of glucose-dependent insulinotropic polypeptide analogue. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd.
Okamoto, Ryo Isoe, Madoka Izumi, Masayuki Kajihara, Yasuhiro England J Pept Sci. 2016 May;22(5):343-51. doi: 10.1002/psc.2872. Epub 2016 Mar 22.
The following values have no corresponding Zotero field: auth-address: Graduate School of Science, Department of Chemistry, Osaka University, 1-1, Machikaneyama, Toyonaka, Osaka, Japan. alt-title: Journal of peptide science : an official publication of the European Peptide Society number: 5 edition: 2016/03/24 accession-num: 27005965
Keywords: Hydrogen-Ion Concentration; Esters/chemistry; Molecular Structure; Peptides/*chemical synthesis/chemistry; Solid-Phase Synthesis Techniques/*methods

n->p* interactions are competitive with hydrogen bonds - Newberry, R. W.; Orke, S. J.; Raines, R. T. (Org. Lett., 2016)
Because carbonyl groups can participate in both hydrogen bonds and n-->pi* interactions, these two interactions likely affect one another. Herein, enhancement of an amidic n-->pi* interaction is shown to reduce the ability of beta-keto amides to tautomerize to the enol, indicating decreased hydrogen-bonding capacity of the amide carbonyl group. Thus, an n-->pi* interaction can have a significant effect on the strength of a hydrogen bond to the same carbonyl group.
P41 GM103399/GM/NIGMS NIH HHS/United States R01 AR044276/AR/NIAMS NIH HHS/United States T32 GM008349/GM/NIGMS NIH HHS/United States Journal Article United States
The following values have no corresponding Zotero field: auth-address: Department of Chemistry and double daggerDepartment of Biochemistry, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States. Department of Chemistry and double daggerDepartment of Biochemistry, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States. Department of Chemistry and double daggerDepartment of Biochemistry, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States. alt-title: Organic letters number: 15 accession-num: 27409515

Palladium-assisted removal of a solubilizing tag from a Cys side chain to facilitate peptide and protein synthesis - Maity, Suman Kumar; Mann, Guy; Jbara, Muhammad; Laps, Shay; Kamnesky, Guy; Brik, Ashraf (Org. Lett., 2016)
The following values have no corresponding Zotero field: number: 12 publisher: American Chemical Society

Efficient palladium-assisted one-pot deprotection of (acetamidomethyl)cysteine following native chemical ligation and/or desulfurization to expedite chemical protein synthesis - Maity, S. K.; Jbara, M.; Laps, S.; Brik, A. (Angew. Chem. Int. Ed., 2016)
The acetamidomethyl (Acm) moiety is a widely used cysteine protecting group for the chemical synthesis and semisynthesis of peptide and proteins. However, its removal is not straightforward and requires harsh reaction conditions and additional purification steps before and after the removal step, which extends the synthetic process and reduces the overall yield. To overcome these shortcomings, a method for rapid and efficient Acm removal using Pd(II) complexes in aqueous medium is reported. We show, for the first time, the assembly of three peptide fragments in a one-pot fashion by native chemical ligation where the Acm moiety was used to protect the N-terminal Cys of the middle fragment. Importantly, an efficient synthesis of the ubiquitin-like protein UBL-5, which contains two native Cys residues, was accomplished through the one-pot operation of three key steps, namely ligation, desulfurization, and Acm deprotection, highlighting the great utility of the new approach in protein synthesis.
Journal Article Germany
The following values have no corresponding Zotero field: auth-address: Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008, Israel. Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008, Israel. Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008, Israel. Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008, Israel. abrik@technion.ac.il. alt-title: Angewandte Chemie (International ed number: 28 accession-num: 27126503

Peptide-tags for site-specific protein labelling in vitro and in vivo - Lotze, J.; Reinhardt, U.; Seitz, O.; Beck-Sickinger, A. G. (Mol. Biosyst., 2016)
Peptide-tag based labelling can be achieved by (i) enzymes (ii) recognition of metal ions or small molecules and (iii) peptide-peptide interactions and enables site-specific protein visualization to investigate protein localization and trafficking.
Journal Article Review England
The following values have no corresponding Zotero field: auth-address: Institut fur Biochemie, Universitat Leipzig, Bruderstrasse 34, D-04103 Leipzig, Germany. abeck-sickinger@uni-leipzig.de. Institut fur Chemie, Humboldt-Universitat zu Berlin, Brook-Taylor-Strasse 2, D-12489 Berlin, Germany. oliver.seitz@chemie.hu-berlin.de. Institut fur Chemie, Humboldt-Universitat zu Berlin, Brook-Taylor-Strasse 2, D-12489 Berlin, Germany. oliver.seitz@chemie.hu-berlin.de. Institut fur Biochemie, Universitat Leipzig, Bruderstrasse 34, D-04103 Leipzig, Germany. abeck-sickinger@uni-leipzig.de. alt-title: Molecular bioSystems number: 6 accession-num: 26960991
Keywords: Animals; Humans; *Staining and Labeling; Catalysis; Enzymes/chemistry/metabolism; Ions/chemistry/metabolism; Metals/chemistry/metabolism; Peptides/*chemistry/metabolism; Protein Binding; Proteins/*chemistry/metabolism

Total chemical synthesis of proteins without HPLC purification - Loibl, S. F.; Harpaz, Z.; Zitterbart, R.; Seitz, O. (Chem. Sci., 2016)
The total chemical synthesis of proteins is a tedious and time-consuming endeavour. The typical steps involve solid phase synthesis of peptide thioesters and cysteinyl peptides, native chemical ligation (NCL) in solution, desulfurization or removal of ligation auxiliaries in the case of extended NCL as well as many intermediary and final HPLC purification steps. With an aim to facilitate and improve the throughput of protein synthesis we developed the first method for the rapid chemical total on-resin synthesis of proteins that proceeds without a single HPLC-purification step. The method relies on the combination of three orthogonal protein tags that allow sequential immobilization (via the N-terminal and C-terminal ends), extended native chemical ligation and release reactions. The peptide fragments to be ligated are prepared by conventional solid phase synthesis and used as crude materials in the subsequent steps. An N-terminal His6 unit permits selective immobilization of the full length peptide thioester onto Ni-NTA agarose beads. The C-terminal peptide fragment carries a C-terminal peptide hydrazide and an N-terminal 2-mercapto-2-phenyl-ethyl ligation auxiliary, which serves as a reactivity tag for the full length peptide. As a result, only full length peptides, not truncation products, react in the subsequent on-bead extended NCL. After auxiliary removal the ligation product is liberated into solution upon treatment with mild acid, and is concomitantly captured by an aldehyde-modified resin. This step allows the removal of the most frequently observed by-product in NCL chemistry, i.e. the hydrolysed peptide thioester (which does not contain a C-terminal peptide hydrazide). Finally, the target protein is released with diluted hydrazine or acid. We applied the method in the synthesis of 46 to 126 amino acid long MUC1 proteins comprising 2-6 copies of a 20mer tandem repeat sequence. Only three days were required for the parallel synthesis of 9 MUC1 proteins which were obtained in 8-33% overall yield with 90-98% purity despite the omission of HPLC purification.
2041-6520 10.1039/C6SC01883A
The following values have no corresponding Zotero field: number: 11 publisher: The Royal Society of Chemistry

a-Azido acids in solid-phase peptide synthesis: Compatibility with Fmoc chemistry and an alternative approach to the solid Phase synthesis of Daptomycin analogs - Lohani, Chuda Raj; Rasera, Benjamin; Scott, Bradley; Palmer, Michael; Taylor, Scott D. (J. Org. Chem., 2016)
doi: 10.1021/acs.joc.5b02882 0022-3263 doi: 10.1021/acs.joc.5b02882
The following values have no corresponding Zotero field: number: 6 publisher: American Chemical Society

Native chemical ligation strategy to overcome side reactions during Fmoc-based synthesis of C-terminal cysteine-containing peptides - Lelièvre, Dominique; Terrier, Victor P.; Delmas, Agnès F.; Aucagne, Vincent (Org. Lett., 2016)
The following values have no corresponding Zotero field: number: 5 publisher: American Chemical Society

Palladium mediated rapid deprotection of N-terminal cysteine under native chemical ligation conditions for the efficient preparation of synthetically challenging proteins - Jbara, M.; Maity, S. K.; Seenaiah, M.; Brik, A. (J. Am. Chem. Soc., 2016)
Facilitating the process of chemical protein synthesis is an important goal in order to enable the efficient preparation of large and novel protein analogues. Native chemical ligation, which is widely used in the synthesis and semisynthesis of proteins, has been going through several developments to expedite the synthetic process and to obtain the target protein in high yield. A key aspect of this approach is the utilization of protecting groups for the N-terminal Cys in the middle fragments, which bear simultaneously the two reactive groups, i.e., N-terminal Cys and C-terminal thioester. Despite important progress in this area, as has been demonstrated in the use of thiazolidine protecting group in the synthesis of over 100 proteins, finding optimal protecting group(s) remains a challenge. For example, the thiazolidine removal step is very slow (>8 h), and in some cases the applied conditions lead to undesired side reactions. Here we show that water-soluble palladium(II) complexes are excellent reagents for the effective unmasking of thiazolidine, enabling its complete removal within 15 min under native chemical ligation conditions. Moreover, palladium is also able to rapidly remove propargyloxycarbonyl-protecting group from the N-terminal Cys in a similar efficiency. The utility of the new removal conditions for both protecting groups is exemplified in the rapid and efficient synthesis of Lys34-ubiquitinated H2B and for the first time neddlyated peptides derived from cullin1. The current approach expands the use of palladium in protein chemistry and should significantly facilitate the chemical and semisynthesis of synthetically challenging proteins from multiple fragments.
Journal Article Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: Schulich Faculty of Chemistry, Technion-Israel Institute of Technology , Haifa, 3200008, Israel. Schulich Faculty of Chemistry, Technion-Israel Institute of Technology , Haifa, 3200008, Israel. Schulich Faculty of Chemistry, Technion-Israel Institute of Technology , Haifa, 3200008, Israel. Schulich Faculty of Chemistry, Technion-Israel Institute of Technology , Haifa, 3200008, Israel. alt-title: Journal of the American Chemical Society number: 15 accession-num: 27023072
Keywords: Amino Acid Sequence; Cysteine/*chemistry; Molecular Sequence Data; Palladium/*chemistry; Proteins/*chemical synthesis; Thiazolidines/chemistry

Chemical synthesis of phosphorylated histone H2A at Tyr57 reveals insight into the inhibition mode of the SAGA deubiquitinating module - Jbara, M.; Maity, S. K.; Morgan, M.; Wolberger, C.; Brik, A. (Angew. Chem. Int. Ed., 2016)
Monoubiquitination of histone H2B plays a central role in transcription activation and is required for downstream histone-methylation events. Deubiquitination of H2B by the Spt-Ada-Gcn5 acetyltransferase (SAGA) coactivator complex is regulated by a recently discovered histone mark, phosphorylated H2AY57 (H2AY57p), which inhibits deubiquitination of H2B by the SAGA complex as well as restricting demethylation of H3 and increasing its acetylation. Evidence for the effect of H2AY57p, however, was indirect and was investigated in vivo by monitoring the effects of chemical inhibition of Tyr kinase CK2 or by mutating the phosphorylation site. We applied the total chemical synthesis of proteins to prepare H2AY57p efficiently and study the molecular details of this regulation. This analogue, together with semisynthetically prepared ubiquitinated H2B, enabled us to provide direct evidence for the cross-talk between those two marks and the inhibition of SAGA activity by H2AY57p.
Jbara, Muhammad Maity, Suman Kumar Morgan, Michael Wolberger, Cynthia Brik, Ashraf R01 GM095822/GM/NIGMS NIH HHS/ GM-095822/GM/NIGMS NIH HHS/ Germany International ed. in English Angew Chem Int Ed Engl. 2016 Apr 11;55(16):4972-6. doi: 10.1002/anie.201600638. Epub 2016 Mar 9.
The following values have no corresponding Zotero field: auth-address: Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008, Israel. Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD, 21205-2185, USA. Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD, 21205-2185, USA. cwolberg@jhmi.edu. Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008, Israel. abrik@technion.ac.il. number: 16 edition: 2016/03/10 accession-num: 26960207 work-type: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Keywords: Amino Acid Sequence; Acetylation; Chromatography, High Pressure Liquid; Histones/*chemistry; Mass Spectrometry; Phosphorylation; Tyrosine/*chemistry; Ubiquitin/*chemistry

Synthesis of l- and d-ubiquitin by one-pot ligation and metal-free desulfurization - Huang, Yi-Chao; Chen, Chen-Chen; Gao, Shuai; Wang, Ye-Hai; Xiao, Hua; Wang, Feng; Tian, Chang-Lin; Li, Yi-Ming (Chem. Eur. J., 2016)
Native chemical ligation combined with desulfurization has become a powerful strategy for the chemical synthesis of proteins. Here we describe the use of a new thiol additive, methyl thioglycolate, to accomplish one-pot native chemical ligation and metal-free desulfurization for chemical protein synthesis. This one-pot strategy was used to prepare ubiquitin from two or three peptide segments. Circular dichroism spectroscopy and racemic protein X-ray crystallography confirmed the correct folding of ubiquitin. Our results demonstrate that proteins synthesized chemically by streamlined 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis coupled with a one-pot ligation–desulfurization strategy can supply useful molecules with sufficient purity for crystallographic studies.
1521-3765
The following values have no corresponding Zotero field: number: 22
Keywords: native chemical ligation; proteins; desulfurization; methyl thioglycolate; X-ray diffraction

FRET-based cyanine probes for monitoring ligation reactions and their applications to mechanistic studies and catalyst screening - Herbst, E.; Shabat, D. (Org. Biomol. Chem., 2016)
There is an ever-increasing need to design better methods to selectively connect two molecules under mild aqueous conditions on a small scale. The process of finding such methods significantly relies on the employment of an appropriate assay. We report here a modular FRET-based assay to monitor such reactions and illustrate how the assay is used to monitor two particular reactions: native chemical ligation (NCL) and oxime ligation. For both reactions we show that by employing appropriately designed probes FRET measurements could be used to monitor the reaction's progress. We additionally demonstrate the usefulness of the developed probe system to study the mechanisms of the ligation reactions, for example, in monitoring the formation of a trimeric intermediate in the NCL reaction. Finally, we demonstrate that FRET measurements conducted in our system allow the quantification of the reaction yield and we show the application of our FRET-based assay to catalyst screening for the oxime ligation.
1477-0520 10.1039/C5OB02127H
The following values have no corresponding Zotero field: number: 15 publisher: The Royal Society of Chemistry

Native chemical ligation at a base-labile 4-mercaptobutyrate N(alpha)-auxiliary - Harpaz, Z.; Loibl, S.; Seitz, O. (Bioorg. Med. Chem. Lett., 2016)
Native chemical ligation (NCL) proceeds via a S-N acyl shift and, therefore, requires N-terminal cysteine. N(alpha)-auxiliaries have long been used to enable NCL beyond cysteine. However, the reversibility of the S-N acyl shift under the acidic conditions used to remove the commonly applied N-benzyl auxiliaries limits the scope of this reaction. Herein, we introduce a new class of N(alpha)-auxiliary which is designed for removal under mild basic conditions. The 3-N-linked 4-mercaptobutyrate auxiliary is readily synthesized in a single step and enables introduction on solid phase by means of reductive amination. The usefulness of the new auxiliary was demonstrated in the synthesis of the anti-microbial C-terminal domain of Dermicidine-1L.
Journal Article England
The following values have no corresponding Zotero field: auth-address: Institut fur Chemie, Humboldt Universitat zu Berlin, Brook-Taylor-Strasse 2, 12489 Berlin, Germany. Institut fur Chemie, Humboldt Universitat zu Berlin, Brook-Taylor-Strasse 2, 12489 Berlin, Germany. Institut fur Chemie, Humboldt Universitat zu Berlin, Brook-Taylor-Strasse 2, 12489 Berlin, Germany. alt-title: Bioorganic & medicinal chemistry letters number: 5 accession-num: 26838809

Internal activation of peptidyl prolyl thioesters in native chemical ligation - Gui, Y.; Qiu, L.; Li, Y.; Li, H.; Dong, S. (J. Am. Chem. Soc., 2016)
Prolyl thioesters have shown significantly lower reactivities in native chemical ligation (NCL) in comparison to that of the alanyl thioester. This report describes a mild and efficient internal activation protocol of peptidyl prolyl thioesters in NCL without using any thiol-based additives, where the introduction of a 4-mercaptan substituent on the C-terminal proline significantly improves the reactivity of prolyl thioesters via the formation of a bicyclic thiolactone intermediate. The kinetic data indicate that the reaction rate is comparable to that of the reported data of alanyl thioesters, and the mechanistic studies suggest that the ligation of two peptide segments proceeds through an NCL-like pathway instead of a direct aminolysis, which ensures the chemoselectivity and compatibility of various amino acid side chains. This 4-mercaptoprolyl thioester-based protocol also allows an efficient one-pot ligation-desulfurization procedure. The utility of this method has been further demonstrated in the synthesis of a proline-rich region of Wilms tumor protein 1.
Journal Article Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , 38 Xueyuan Road, Haidian District, Beijing 100191, China. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , 38 Xueyuan Road, Haidian District, Beijing 100191, China. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , 38 Xueyuan Road, Haidian District, Beijing 100191, China. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , 38 Xueyuan Road, Haidian District, Beijing 100191, China. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , 38 Xueyuan Road, Haidian District, Beijing 100191, China. alt-title: Journal of the American Chemical Society number: 14 accession-num: 26982082

Visible-light-induced specific desulfurization of cysteinyl peptide and glycopeptide in aqueous solution - Gao, Xiao-Fei; Du, Jing-Jing; Liu, Zheng; Guo, Jun (Org. Lett., 2016)
doi: 10.1021/acs.orglett.6b00292 1523-7060 doi: 10.1021/acs.orglett.6b00292
The following values have no corresponding Zotero field: number: 5 publisher: American Chemical Society

Monomer/oligomer quasi-racemic protein crystallography - Gao, Shuai; Pan, Man; Zheng, Yong; Huang, Yichao; Zheng, Qingyun; Sun, Demeng; Lu, Lining; Tan, Xiaodan; Tan, Xianglong; Lan, Huan; Wang, Jiaxing; Wang, Tian; et al. (J. Am. Chem. Soc., 2016)
The following values have no corresponding Zotero field: number: 43 publisher: American Chemical Society

Development of an anilide-type scaffold for the thioester precursor N-sulfanylethylcoumarinyl amide - Eto, M.; Naruse, N.; Morimoto, K.; Yamaoka, K.; Sato, K.; Tsuji, K.; Inokuma, T.; Shigenaga, A.; Otaka, A. (Org. Lett., 2016)
N-Sulfanylethylcoumarinyl amide (SECmide) peptide, which was initially developed for use in the fluorescence-guided detection of promoters of N-S acyl transfer, was successfully applied to a facile and side reaction-free protocol for N-S acyl-transfer-mediated synthesis of peptide thioesters. Additionally, 4-mercaptobenzylphosphonic acid (MBPA) was proven to be a useful catalyst for the SECmide or N-sulfanylethylanilide (SEAlide)-mediated NCL reaction.
Journal Article United States
The following values have no corresponding Zotero field: auth-address: Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University , Tokushima 770-8505, Japan. Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University , Tokushima 770-8505, Japan. Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University , Tokushima 770-8505, Japan. Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University , Tokushima 770-8505, Japan. Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University , Tokushima 770-8505, Japan. Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University , Tokushima 770-8505, Japan. Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University , Tokushima 770-8505, Japan. Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University , Tokushima 770-8505, Japan. PRESTO, Japan Science and Technology Agency (JST) , Kawaguchi, Saitama 332-0012, Japan. Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University , Tokushima 770-8505, Japan. alt-title: Organic letters number: 17 accession-num: 27529363

Convergent synthesis of N-linked glycopeptides via aminolysis of ω-Asp p-nitrophenyl thioesters in solution - Du, Jing-Jing; Gao, Xiao-Fei; Xin, Ling-Ming; Lei, Ze; Liu, Zheng; Guo, Jun (Org. Lett., 2016)
An efficient N-linked glycosylation reaction between glycosylamines and p-nitrophenyl thioester peptides has been developed. The reaction conditions are mild and compatible with the C-terminal free carboxylic acid group and the unprotected N-linked sialyloligosaccharide. By means of this convergent strategy, a versatile N-glycopeptide fragment containing an N-terminal Thz and a C-terminal thioester was readily prepared, which is available for the synthesis of long glycopeptides and glycoproteins using the protocol of native chemical ligation.
The following values have no corresponding Zotero field: number: 19 publisher: American Chemical Society

A central cysteine residue is essential for the thermal stability and function of SUMO-1 protein and SUMO-1 peptide-protein conjugates - Drobecq, H.; Boll, E.; Senechal, M.; Desmet, R.; Saliou, J. M.; Lacapere, J. J.; Mougel, A.; Vicogne, J.; Melnyk, O. (Bioconjugate Chem., 2016)
SUMOylation constitutes a major post-translational modification (PTM) used by the eukaryote cellular machinery to modulate protein interactions of the targeted proteins. The small ubiquitin-like modifier-1 (SUMO-1) features a central and conserved cysteine residue (Cys52) that is located in the hydrophobic core of the protein and in tight contact with Phe65, suggesting the occurrence of an S/pi interaction. To investigate the importance of Cys52 on SUMO-1 thermal stability and biochemical properties, we produced by total chemical synthesis SUMO-1 or SUMO-1 Cys52Ala peptide-protein conjugates featuring a native isopeptidic bond between SUMO-1 and a peptide derived from p53 tumor suppressor protein. The Cys52Ala modification perturbed SUMO-1 secondary structure and resulted in a dramatic loss of protein thermal stability. Moreover, the cleavage of the isopeptidic bond by the deconjugating enzyme Upl1 was significantly less efficient than for the wild-type conjugate. Similarly, the in vitro SUMOylation of RanGap1 by E1/E2 conjugating enzymes was significantly less efficient with the SUMO-1 C52A analog compared to wild-type SUMO-1. These data demonstrate the critical role of Cys52 in maintaining SUMO-1 conformation and function and the importance of keeping this cysteine intact for the study of SUMO-1 protein conjugates.
Cited By :11
Cited By :11
Cited By :11
Export Date: 25 May 2018
Export Date: 25 May 2018

Efficient total chemical synthesis of (13) C=(18) O isotopomers of human insulin for isotope-edited FTIR - Dhayalan, B.; Fitzpatrick, A.; Mandal, K.; Whittaker, J.; Weiss, M. A.; Tokmakoff, A.; Kent, S. B. H. (ChemBioChem, 2016)
Isotope-edited two-dimensional Fourier transform infrared spectroscopy (2 D FTIR) can potentially provide a unique probe of protein structure and dynamics. However, general methods for the site-specific incorporation of stable (13) C=(18) O labels into the polypeptide backbone of the protein molecule have not yet been established. Here we describe, as a prototype for the incorporation of specific arrays of isotope labels, the total chemical synthesis-via a key ester insulin intermediate-of 97 % enriched [(1-(13) C=(18) O)Phe(B24) ] human insulin: stable-isotope labeled at a single backbone amide carbonyl. The amino acid sequence as well as the positions of the disulfide bonds and the correctly folded structure were unambiguously confirmed by the X-ray crystal structure of the synthetic protein molecule. In vitro assays of the isotope labeled [(1-(13) C=(18) O)Phe(B24) ] human insulin showed that it had full insulin receptor binding activity. Linear and 2 D IR spectra revealed a distinct red-shifted amide I carbonyl band peak at 1595 cm(-1) resulting from the (1-(13) C=(18) O)Phe(B24) backbone label. This work illustrates the utility of chemical synthesis to enable the application of advanced physical methods for the elucidation of the molecular basis of protein function.
R01 DK040949/DK/NIDDK NIH HHS/United States R01 DK089934/DK/NIDDK NIH HHS/United States R01K08993/PHS HHS/United States RR-15301/RR/NCRR NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Germany a European journal of chemical biology
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL, 60637, USA. Department of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL, 60637, USA. The James Frank Institute, University of Chicago, 929 East 57th Street, Chicago, IL, 60637, USA. Department of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL, 60637, USA. Department of Biochemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA. Department of Biochemistry, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA. Department of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL, 60637, USA. tokmakoff@uchicago.edu. The James Frank Institute, University of Chicago, 929 East 57th Street, Chicago, IL, 60637, USA. tokmakoff@uchicago.edu. Department of Chemistry, Institute for Biophysical Dynamics, The University of Chicago, 929 East 57th Street, Chicago, IL, 60637, USA. skent@uchicago.edu. number: 5 accession-num: 26715336
Keywords: Amino Acid Sequence; Humans; Molecular Sequence Data; Carbon Isotopes/*chemistry; Insulin/*chemistry; Oxygen Isotopes/*chemistry; Spectroscopy, Fourier Transform Infrared/*methods

Nonclassical routes for amide bond formation - de Figueiredo, Renata Marcia; Suppo, Jean-Simon; Campagne, Jean-Marc (Chem. Rev., 2016)
The following values have no corresponding Zotero field: number: 19 publisher: American Chemical Society

Nonenzymatic biomimetic remodeling of phospholipids in synthetic liposomes - Brea, R. J.; Rudd, A. K.; Devaraj, N. K. (Proc. Natl. Acad. Sci. U. S. A., 2016)
Cell membranes have a vast repertoire of phospholipid species whose structures can be dynamically modified by enzymatic remodeling of acyl chains and polar head groups. Lipid remodeling plays important roles in membrane biology and dysregulation can lead to disease. Although there have been tremendous advances in creating artificial membranes to model the properties of native membranes, a major obstacle has been developing straightforward methods to mimic lipid membrane remodeling. Stable liposomes are typically kinetically trapped and are not prone to exchanging diacylphospholipids. Here, we show that reversible chemoselective reactions can be harnessed to achieve nonenzymatic spontaneous remodeling of phospholipids in synthetic membranes. Our approach relies on transthioesterification/acyl shift reactions that occur spontaneously and reversibly between tertiary amides and thioesters. We demonstrate exchange and remodeling of both lipid acyl chains and head groups. Using our synthetic model system we demonstrate the ability of spontaneous phospholipid remodeling to trigger changes in vesicle spatial organization, composition, and morphology as well as recruit proteins that can affect vesicle curvature. Membranes capable of chemically exchanging lipid fragments could be used to help further understand the specific roles of lipid structure remodeling in biological membranes.
Journal Article United States
The following values have no corresponding Zotero field: auth-address: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093. Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093. Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093 ndevaraj@ucsd.edu. alt-title: Proceedings of the National Academy of Sciences of the United States of America number: 31 accession-num: 27439858

Expanding the chemical toolbox for the synthesis of large and uniquely modified proteins - Bondalapati, S.; Jbara, M.; Brik, A. (Nat. Chem., 2016)
Methods to prepare proteins that include a specific modification at a desired position are essential for understanding their cellular functions and physical properties in living systems. Chemical protein synthesis, which relies on the chemoselective ligation of unprotected peptides, enables the preparation of modified proteins that are not easily fabricated by other methods. In contrast to recombinant approaches, chemical synthesis can be used to prepare protein analogues such as D-proteins, which are useful in protein structure determination and the discovery of novel therapeutics. Post-translationally modifying proteins is another example where chemical protein synthesis proved itself as a powerful approach for preparing samples with high homogeneity and in workable quantities. In this Review, we discuss the basic principles of the field, focusing on novel chemoselective peptide ligation approaches such as native chemical ligation and the recent advances based on this method with a proven record of success in the synthesis of highly important protein targets.
Bondalapati, Somasekhar Jbara, Muhammad Brik, Ashraf England Nat Chem. 2016 Apr 22;8(5):407-18. doi: 10.1038/nchem.2476.
The following values have no corresponding Zotero field: auth-address: Schulich Faculty of Chemistry, Technion - Israel Institute of Technology, 3200008 Haifa, Israel. alt-title: Nature chemistry number: 5 edition: 2016/04/23 accession-num: 27102674 work-type: Review

Kinetically Controlled Chemoselective Cyclization Simplifies the Access to Cyclic and Branched Peptides - Boll, E.; Drobecq, H.; Lissy, E.; Cantrelle, F. X.; Melnyk, O. (Org. Lett., 2016)
A bis(2-sulfanylethyl)amido group reacts significantly faster with cysteinyl peptides when installed on the C-terminal end of a peptide in comparison with the side-chain of Asp and Glu. This property enabled the design of a kinetically controlled chemoselective peptide cyclization reaction, giving straightforward access to cyclic and branched peptides in one pot.
Cited By :5
Cited By :5
Export Date: 25 May 2018
Export Date: 25 May 2018
Journal article

Advances in Fmoc solid-phase peptide synthesis - Behrendt, Raymond; White, Peter; Offer, John (J. Pept. Sci., 2016)
Today, Fmoc SPPS is the method of choice for peptide synthesis. Very‐high‐quality Fmoc building blocks are available at low cost because of the economies of scale arising from current multiton production of therapeutic peptides by Fmoc SPPS. Many modified derivatives are commercially available as Fmoc building blocks, making synthetic access to a broad range of peptide derivatives straightforward. The number of synthetic peptides entering clinical trials has grown continuously over the last decade, and recent advances in the Fmoc SPPS technology are a response to the growing demand from medicinal chemistry and pharmacology. Improvements are being continually reported for peptide quality, synthesis time and novel synthetic targets. Topical peptide research has contributed to a continuous improvement and expansion of Fmoc SPPS applications. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.
PSC2836[PII] 26785684[pmid] J Pept Sci
The following values have no corresponding Zotero field: number: 1 pub-location: Hoboken publisher: John Wiley and Sons Inc. accession-num: PMC4745034

Mechanism for the enhanced reactivity of 4-mercaptoprolyl thioesters in native chemical ligation - Ali Shah, Muhammad Ishaq; Xu, Zhe-Yuan; Liu, Lei; Jiang, Yuan-Ye; Shi, Jing (RSC Adv., 2016)
The introduction of a 4-mercaptan substituent was recently reported to be effective to improve the reactivity of C-terminal prolyl thioesters in native chemical ligation (NCL). To elucidate the origin of the high reactivity of 4-mercaptoprolyl thioesters, a theoretical study was performed on the transthioesterification of NCL herein with the aid of density functional theory (DFT) methods. The calculation results support a transthioesterification mechanism involving two stages. The first stage is the intramolecular transthioesterification of 4-mercaptoprolyl thioesters to form a bicyclic thiolactone intermediate and the second stage is the intermolecular transthioesterification of the thiolactone intermediate with N-terminal cysteine. The two stages proceed both via nucleophilic attack of the thiolate and proton-donor-assisted thiolate release. The thiolate release in the first stage is the rate-determining step of the whole transthioesterification of 4-mercaptoprolyl thioesters. Based on the mechanistic details, further analysis was conducted to gain a deeper insight with natural bond orbital (NBO) analysis, non-covalent interaction plots (NCIplots), distortion analysis, etc. The n [rightward arrow] [small pi]* interaction between the N-carbonyl oxygen and thioester carbonyl was found to be detrimental to the first stage while a previously unnoticed n [rightward arrow] [small pi]* interaction between the amide nitrogen and the thiolactone carbonyl slightly benefits the second stage. The entropy effect was the main driving force for the first stage because this stage is an intramolecular one-to-two process overall. On the other hand, the release of the ring stain precluded in the bicyclic thiolactone intermediate is mainly responsible for the high reactivity of the thiolactone in the second stage compared with other prolyl thioesters. Meanwhile, the intramolecular hydrogen bond between the thiolactone carbonyl oxygen and the protonated amine of N-terminal cysteine also contributes to the transthioesterification.
10.1039/C6RA13793H
The following values have no corresponding Zotero field: number: 72 publisher: The Royal Society of Chemistry

One-pot/sequential native chemical ligation using photocaged crypto-thioester - Aihara, K.; Yamaoka, K.; Naruse, N.; Inokuma, T.; Shigenaga, A.; Otaka, A. (Org. Lett., 2016)
A practical and efficient methodology for the chemical synthesis of peptides/proteins using a one-pot/sequential ligation is described. It features the use of photocleavable S-protection on an N-sulfanylethylaniline moiety. Removal of the S-protecting ligated materials under UV irradiation provides a readily usable mixture for subsequent native chemical ligation.
Journal Article Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University , 1-78-1 Shomachi, Tokushima 770-8505, Japan. Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University , 1-78-1 Shomachi, Tokushima 770-8505, Japan. Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University , 1-78-1 Shomachi, Tokushima 770-8505, Japan. Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University , 1-78-1 Shomachi, Tokushima 770-8505, Japan. Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University , 1-78-1 Shomachi, Tokushima 770-8505, Japan. Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University , 1-78-1 Shomachi, Tokushima 770-8505, Japan. alt-title: Organic letters number: 3 accession-num: 26753720
Keywords: Molecular Structure; Peptides/*chemical synthesis/chemistry; Ligation; Photochemical Processes; Sulfur Compounds/*chemistry; Ultraviolet Rays

A backbone amide protecting group for overcoming difficult sequences and suppressing aspartimide formation - Abdel-Aal, A. B.; Papageorgiou, G.; Raz, R.; Quibell, M.; Burlina, F.; Offer, J. (J Pept Sci, 2016)
A backbone amide bond protecting group, 2-hydroxy-4-methoxy-5-nitrobenzyl (Hmnb), improved the synthesis of aggregation and aspartimide-prone peptides. Introduction of Hmnb is automated and carried out during peptide assembly by addition of 4-methoxy-5-nitrosalicylaldehyde to the peptidyl-resin and on-resin reduction to the secondary amine. Acylation of the hindered secondary amine is aided by the formation of an internal nitrophenol ester that undergoes a favourable O,N intramolecular acyl transfer. This activated ester participates in the coupling and generally gives complete reaction with standard coupling conditions. Hmnb is easily available in a single preparative step from commercially available material. Different methods for removing the amide protecting group were explored. The protecting group is labile to acidolysis, following reduction of the nitro group to the aniline. The two main uses of backbone protection of preventing aspartimide formation and of overcoming difficult sequences are demonstrated, first with the synthesis of a challenging aspartimide-prone test sequence and then with the classic difficult sequence ACP (65-74) and a 23-mer homopolymer of polyalanine.
Abdel-Aal, Abu-Baker M Papageorgiou, George Raz, Richard Quibell, Martin Burlina, Fabienne Offer, John MRC_MC_U117592730/Medical Research Council/United Kingdom England J Pept Sci. 2016 May;22(5):360-7. doi: 10.1002/psc.2877. Epub 2016 Apr 18.
The following values have no corresponding Zotero field: auth-address: The Francis Crick Institute, Mill Hill Laboratory, The Ridgeway, London, NW7 1AA, UK. Sorbonne Universites, UPMC Universite Paris 06, LBM, 4 place Jussieu, 75005, Paris, France. CNRS, UMR 7203, LBM, Paris, France. Departement de Chimie, LBM, ENS, PSL Research University, 24 Rue Lhomond, 75005, Paris, France. alt-title: Journal of peptide science : an official publication of the European Peptide Society number: 5 edition: 2016/04/19 accession-num: 27086749
Keywords: Amino Acid Sequence; Molecular Structure; Peptides/*chemical synthesis/chemistry; Acylation; Amides/*chemistry; Aspartic Acid/*analogs & derivatives/chemistry; Nitrobenzenes/chemistry; Solid-Phase Synthesis Techniques

The I-TASSER Suite: protein structure and function prediction - Yang, J.; Yan, R.; Roy, A.; Xu, D.; Poisson, J.; Zhang, Y. (Nat. Methods, 2015)
R01 GM083107/GM/NIGMS NIH HHS/United States R01 GM084222/GM/NIGMS NIH HHS/United States GM083107/GM/NIGMS NIH HHS/United States GM084222/GM/NIGMS NIH HHS/United States Letter Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. United States
The following values have no corresponding Zotero field: auth-address: Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA. 1] Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, USA. alt-title: Nature methods number: 1 accession-num: 25549265
Keywords: Amino Acid Sequence; *Models, Molecular; *Molecular Structure; Proteins/*chemistry; Sequence Alignment; Software

Synthesis and folding of a mirror-image enzyme reveals ambidextrous chaperone activity - Weinstock, M. T.; Jacobsen, M. T.; Kay, M. S. (Proc. Natl. Acad. Sci. U. S. A., 2015)
Mirror-image proteins (composed of D-amino acids) are promising therapeutic agents and drug discovery tools, but as synthesis of larger D-proteins becomes feasible, a major anticipated challenge is the folding of these proteins into their active conformations. In vivo, many large and/or complex proteins require chaperones like GroEL/ES to prevent misfolding and produce functional protein. The ability of chaperones to fold D-proteins is unknown. Here we examine the ability of GroEL/ES to fold a synthetic d-protein. We report the total chemical synthesis of a 312-residue GroEL/ES-dependent protein, DapA, in both L- and D-chiralities, the longest fully synthetic proteins yet reported. Impressively, GroEL/ES folds both L- and D-DapA. This work extends the limits of chemical protein synthesis, reveals ambidextrous GroEL/ES folding activity, and provides a valuable tool to fold d-proteins for drug development and mirror-image synthetic biology applications.
AI076168/AI/NIAID NIH HHS/United States AI102347/AI/NIAID NIH HHS/United States F31CA171677/CA/NCI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural United States
The following values have no corresponding Zotero field: auth-address: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650. Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650. Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650 kay@biochem.utah.edu. alt-title: Proceedings of the National Academy of Sciences of the United States of America number: 32 accession-num: 25071217
Keywords: Amino Acid Sequence; Models, Molecular; Stereoisomerism; Molecular Sequence Data; *Protein Folding; Amino Acids/chemistry; Biophysical Phenomena; Chaperonin 10/metabolism; Chaperonin 60/metabolism; Enzymes/*biosynthesis/*chemistry/genetics; Escherichia coli Proteins/biosynthesis/chemistry/genetics; Hydro-Lyases/biosynthesis/chemistry/genetics; Molecular Chaperones/*metabolism; Picolinic Acids/metabolism; Protein Structure, Quaternary

Peptide o-aminoanilides as crypto-thioesters for protein chemical synthesis - Wang, J. X.; Fang, G. M.; He, Y.; Qu, D. L.; Yu, M.; Hong, Z. Y.; Liu, L. (Angew. Chem. Int. Ed., 2015)
Fully unprotected peptide o-aminoanilides can be efficiently activated by NaNO2 in aqueous solution to furnish peptide thioesters for use in native chemical ligation. This finding enables the convergent synthesis of proteins from readily synthesizable peptide o-aminoanilides as a new type of crypto-thioesters. The practicality of this approach is shown by the synthesis of histone H2B from five peptide segments. Purification or solubilization tags, which are sometimes needed to improve the efficiency of protein chemical synthesis, can be incorporated into the o-aminoanilide moiety, as demonstrated in the preparation of the cyclic protein lactocyclicin Q.
The following values have no corresponding Zotero field: auth-address: Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 (China). number: 7 edition: 2014/12/06 accession-num: 25475965 work-type: Research Support, Non-U.S. Gov't
Wang, Jia-Xing Fang, Ge-Min He, Yao Qu, Da-Liang Yu, Min Hong, Zhang-Yong Liu, Lei Germany International ed. in English Angew Chem Int Ed Engl. 2015 Feb 9;54(7):2194-8. doi: 10.1002/anie.201408078. Epub 2014 Dec 4.
Keywords: Amino Acid Sequence; Models, Molecular; Molecular Sequence Data; Amination; Anilides/chemical synthesis/*chemistry; Esters; Histones/*chemical synthesis/chemistry; Nitrogen/chemistry; Peptides/chemical synthesis/*chemistry; Sulfhydryl Compounds/chemical synthesis/chemistry

Synthesis of cysteine-rich peptides by native chemical ligation without use of exogenous thiols - Tsuda, Shugo; Yoshiya, Taku; Mochizuki, Masayoshi; Nishiuchi, Yuji (Org. Lett., 2015)
doi: 10.1021/acs.orglett.5b00624 1523-7060 doi: 10.1021/acs.orglett.5b00624
The following values have no corresponding Zotero field: number: 7 publisher: American Chemical Society

Desulfurization mechanism of cysteine in synthesis of polypeptides - Yan Tian; Li Wang; Jing Shi; Hai-zhu Yu (Chin. J. Chem. Phys., 2015)
The following values have no corresponding Zotero field: number: 3
Keywords: Cysteine,Desulfurization,Reaction mechanism,Density functional theory

An efficient one-pot four-segment condensation method for protein chemical synthesis - Tang, Shan; Si, Yan-Yan; Wang, Zhi-Peng; Mei, Kun-Rong; Chen, Xin; Cheng, Jing-Yuan; Zheng, Ji-Shen; Liu, Lei (Angew. Chem. Int. Ed., 2015)
The following values have no corresponding Zotero field: publisher: WILEY-VCH Verlag
Keywords: native chemical ligation; protein chemical synthesis; peptides; protecting groups; solid-phase synthesis

An efficient computational model to predict protonation at the amide nitrogen and reactivity along the C-N rotational pathway - Szostak, Roman; Aube, Jeffrey; Szostak, Michal (Chem. Commun., 2015)
N-Protonation of amides is critical in numerous biological processes, including amide bonds proteolysis and protein folding as well as in organic synthesis as a method to activate amide bonds towards unconventional reactivity. A computational model enabling prediction of protonation at the amide bond nitrogen atom along the C-N rotational pathway is reported. Notably, this study provides a blueprint for the rational design and application of amides with a controlled degree of rotation in synthetic chemistry and biology.
1359-7345 10.1039/C5CC01034A
The following values have no corresponding Zotero field: number: 29 publisher: The Royal Society of Chemistry

The toolbar and its menus - Suzek, B. E.; Yang, Y. Y.; Huang, H.; McGarvey, P. B.; Wu, C. H. (The UniProt Consortium Bioinformatics, 2015)
Keywords: #nosource

Theoretical investigations on the thiol-thioester exchange steps of different thioesters - Sun, Xiao-Hui; Yu, Hai-Zhu; Pei, Shu-Qi; Dang, Zhi-Min (Chin. Chem. Lett., 2015)
Abstract As the rate-determining step in native chemical ligation reactions, the thiol–thioester exchange step is important in determining the efficiency of the ligations of peptides. In the present study, systematic theoretical calculations were carried out on the relationships between the structure of different thioesters and the free energy barriers of the thiol–thioester exchange step. According to the calculation results, the thiol–thioester exchange step is disfavored by the steric hindrance around the carbonyl center, while the electronic effect (i.e. conjugation and hyper-conjugation effects) becomes important when the steric hindrance is insignificant.
1001-8417
The following values have no corresponding Zotero field: number: 10
Keywords: Density functional theory; Native chemical ligation; Thiol–thioester exchange

A stable chemical SUMO1-Ubc9 conjugate specifically binds as a thioester mimic to the RanBP2-E3 ligase complex - Sommer, S.; Ritterhoff, T.; Melchior, F.; Mootz, H. D. (ChemBioChem, 2015)
Ubiquitin and ubiquitin-like (Ubl) modifiers such as SUMO are conjugated to substrate proteins by E1, E2, and E3 enzymes. In the presence of an E3 ligase, the E2 approximately Ubl thioester intermediate becomes highly activated and is prone to chemical decomposition, thus making biochemical and structural studies difficult. Here we explored a stable chemical conjugate of the E2 enzyme from the SUMO pathway, Ubc9, with its modifier SUMO1 as a structural analogue of the Ubc9 approximately SUMO1 thioester intermediate, by introducing a triazole linkage by biorthogonal click chemistry. The chemical conjugate proved stable against proteolytic cleavage, in contrast to a Ubc9-SUMO1 isopeptide analogue obtained by auto-SUMOylation. Triazole-linked Ubc9-SUMO1 bound specifically to the preassembled E3 ligase complex RanBP2/RanGAP1*SUMO1/Ubc9, thus suggesting that it is a suitable thioester mimic. We anticipate interesting prospects for its use as a research tool to study protein complexes involving E2 and E3 enzymes.
Journal Article Research Support, Non-U.S. Gov't Germany a European journal of chemical biology
The following values have no corresponding Zotero field: auth-address: Institute of Biochemistry, University of Muenster, Wilhelm-Klemm-Strasse 2, 48149 Munster (Germany). Zentrum fur Molekulare Biologie der Universitat Heidelberg, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, 69120 Heidelberg (Germany). Zentrum fur Molekulare Biologie der Universitat Heidelberg, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 282, 69120 Heidelberg (Germany). f.melchior@zmbh.uni-heidelberg.de. Institute of Biochemistry, University of Muenster, Wilhelm-Klemm-Strasse 2, 48149 Munster (Germany). henning.mootz@uni-muenster.de. number: 8 accession-num: 25917782
Keywords: Mutation; Catalysis; Protein Binding; Alkynes/chemistry; Azides/chemistry; Copper/chemistry; Cycloaddition Reaction; Hydrolysis; Molecular Chaperones/*chemistry/genetics/metabolism; Nuclear Pore Complex Proteins/*chemistry/genetics/metabolism; Protein Stability; Proteolysis; Substrate Specificity; Sulfhydryl Compounds/*chemistry; SUMO-1 Protein/*chemistry/metabolism; Triazoles/chemistry; Ubiquitin-Conjugating Enzymes/*chemistry/genetics/metabolism; Ubiquitin-Protein Ligases/*chemistry/metabolism

Semi-synthesis of a HGF/SF kringle one (K1) domain scaffold generates a potent in vivo MET receptor agonist - Simonneau, Claire; Berenice, Leclercq; Mougel, Alexandra; Adriaenssens, Eric; Paquet, Charlotte; Raibaut, Laurent; Ollivier, Nathalie; Drobecq, Herve; Marcoux, Julien; Cianferani, Sarah; Tulasne, David; de Jonge, Hugo; et al. (Chem. Sci., 2015)
The development of MET receptor agonists is an important goal in regenerative medicine, but is limited by the complexity and incomplete understanding of its interaction with HGF/SF (Hepatocyte Growth Factor/Scatter Factor). NK1 is a natural occurring agonist comprising the N-terminal (N) and the first kringle (K1) domains of HGF/SF. In the presence of heparin, NK1 can self-associate into a "head to tail" dimer which is considered as the minimal structural module able to trigger MET dimerization and activation whereas isolated K1 and N domains showed a weak or a complete lack of agonistic activity respectively. Starting from these structural and biological observations, we investigated whether it was possible to recapitulate the biological properties of NK1 using a new molecular architecture of isolated N or K1 domains. Therefore, we engineered multivalent N or K1 scaffolds by combining synthetic and homogeneous site-specifically biotinylated N and K1 domains (NB and K1B) and streptavidin (S). NB alone or in complex failed to activate MET signaling and to trigger cellular phenotypes. Importantly and to the contrary of K1B alone, the semi-synthetic K1B/S complex mimicked NK1 MET agonist activity in cell scattering, morphogenesis and survival phenotypic assays. Impressively, K1B/S complex stimulated in vivo angiogenesis and, when injected in mice, protected the liver against fulminant hepatitis in a MET dependent manner whereas NK1 and HGF were substantially less potent. These data reveal that without N domain, proper multimerization of K1 domain is a promising strategy for the rational design of powerful MET agonists.
10.1039/C4SC03856H
Cited By :6
Cited By :6
Cited By :6
Export Date: 25 May 2018

Selective S-deacetylation inspired by native chemical ligation: practical syntheses of glycosyl thiols and drug mercapto-analogues - Shu, Penghua; Zeng, Jing; Tao, Jinyi; Zhao, Yueqi; Yao, Guangmin; Wan, Qian (Green Chem., 2015)
Glycosyl thiols are useful building blocks for the construction of compounds of biological and synthetic importance. Herein, we report a practical synthetic approach toward the efficient synthesis of glycosyl thiols via chemo- and regioselective S-deacetylation inspired by native chemical ligation. This strategy allows the large scale synthesis of glycosyl thiols by simple purification steps without column chromatography. In addition, deacetylation reagents (DTT) could also be recovered and regenerated by a simple process. Thiol containing taxol and artemisinin analogues were successfully prepared based on this methodology. Finally, auranofin, a glucose-based oral drug used to treat rheumatoid arthritis, was synthesized in concise steps and overall high yields.
1463-9262 10.1039/C5GC00084J
The following values have no corresponding Zotero field: number: 4 publisher: The Royal Society of Chemistry

Convergent versus sequential protein synthesis: the case of ubiquitinated and glycosylated H2B - Seenaiah, M.; Jbara, M.; Mali, S. M.; Brik, A. (Angew. Chem. Int. Ed., 2015)
The chemical synthesis of a protein from four fragments or more applying native chemical ligation could be achieved stepwise, in one-pot, convergently, or on a solid support. With the increasing demands of applying protein synthesis to highly complex targets, examining these approaches becomes essential to achieve highly efficient synthesis. Different chemical synthetic strategies are compared for the preparation of the H2B protein having different post-translational modifications. The analogues include H2B that is ubiquitinated at Lys34, Lys120, glycosylated at Ser112, and doubly modified with ubiquitin and N-acetylglucosamine. This study demonstrates that the applied convergent strategy for the synthesis of most of these complex targets was better than the one-pot approach in terms of yield and purity. Some guidelines are offered for future synthetic endeavors of similar challenging proteins.
Journal Article Research Support, Non-U.S. Gov't Germany
The following values have no corresponding Zotero field: auth-address: Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008 (Israel). Department of Chemistry, Ben-Gurion University of the Negev, Beer Sheva, 8410501 (Israel). Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008 (Israel). Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008 (Israel). Department of Chemistry, Ben-Gurion University of the Negev, Beer Sheva, 8410501 (Israel). Schulich Faculty of Chemistry, Technion-Israel Institute of Technology, Haifa, 3200008 (Israel). abrik@technion.ac.il. alt-title: Angewandte Chemie (International ed number: 42 accession-num: 26079184
Keywords: Molecular Conformation; Ubiquitin/*chemistry; Histones/*chemical synthesis/chemistry; *Ubiquitination; Acetylglucosamine/*chemistry; Glycosylation

Acceleration of thiol additive-free native chemical ligation by intramolecular S -> S acyl transfer - Schmalisch, J.; Seitz, O. (Chem. Commun., 2015)
Peptide-mercaptopropionylcysteine (MPA-Cys) thioesters show a surprisingly high reactivity in native chemical ligation (NCL) and allow thiol-additive free reactions. This facilitates sequential NCL reactions and ligation-desulfurization reactions in one-pot formats. The synthetic utility is demonstrated by the synthesis of a SH3 domain.
1359-7345 10.1039/C5CC01447F
The following values have no corresponding Zotero field: number: 35 publisher: The Royal Society of Chemistry

Thiazolidine-protected b-thiol asparagine: Applications in one-pot ligation-desulfurization chemistry - Sayers, Jessica; Thompson, Robert E.; Perry, Kristen J.; Malins, Lara R.; Payne, Richard J. (Org. Lett., 2015)
doi: 10.1021/acs.orglett.5b02468 1523-7060 doi: 10.1021/acs.orglett.5b02468
The following values have no corresponding Zotero field: number: 19 publisher: American Chemical Society

The total chemical synthesis of the monoglycosylated GM2 ganglioside activator using a novel cysteine surrogate - Sato, Kohei; Kitakaze, Keisuke; Nakamura, Takahiro; Naruse, Naoto; Aihara, Keisuke; Shigenaga, Akira; Inokuma, Tsubasa; Tsuji, Daisuke; Itoh, Kohji; Otaka, Akira (Chem. Commun., 2015)
We describe a novel peptide ligation/desulfurization strategy using a [small beta]-mercapto-N-glycosylated asparagine derivative. The newly developed procedure was successfully applied to the total chemical synthesis of the GM2 ganglioside activator protein bearing a monosaccharide on the native glycosylation site.
1359-7345 10.1039/C5CC02967H
The following values have no corresponding Zotero field: number: 49 publisher: The Royal Society of Chemistry

Chemical Protein Synthesis with the KAHA Ligation - Rohrbacher, F.; Wucherpfennig, T. G.; Bode, J. W. (Top. Curr. Chem., 2015)
Since the first report of the chemoselective amide bond forming reaction between alpha-ketoacids and hydroxylamines in 2006, the KAHA (alpha-ketoacid-hydroxylamine) ligation has advanced to a useful tool for the routine synthesis of small to medium sized proteins and cyclic peptides. In this chapter we introduce the concept of KAHA ligation starting with the synthesis and properties of hydroxylamines and alpha-ketoacids, methods for their incorporation into peptides, and give an insight into the mechanism of the KAHA ligation. We cover important improvements including sequential ligations with 5-oxaproline, traceless synthesis of peptide alpha-ketoacids and show their application in chemical protein synthesis and cyclic peptide synthesis. Recent developments of the KAT (potassium acyl trifluoroborate) ligation and its application as fast and chemoselective bioconjugation method are described and an outlook on ongoing work and possible future developments is given at the end of the chapter.
Journal Article Germany
The following values have no corresponding Zotero field: auth-address: Laboratorium fur Organische Chemie, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093, Zurich, Switzerland. alt-title: Topics in current chemistry accession-num: 25761549
Keywords: Molecular Structure; Proteins/*chemical synthesis; Hydroxylamines/*chemistry; Keto Acids/chemical synthesis/chemistry; Protein Engineering

Rapid covalent fluorescence labeling of membrane proteins on live cells via coiled-coil templated acyl transfer - Reinhardt, U.; Lotze, J.; Morl, K.; Beck-Sickinger, A. G.; Seitz, O. (Bioconjugate Chem., 2015)
Fluorescently labeled proteins enable the microscopic imaging of protein localization and function in live cells. In labeling reactions targeted against specific tag sequences, the size of the fluorophore-tag is of major concern. The tag should be small to prevent interference with protein function. Furthermore, rapid and covalent labeling methods are desired to enable the analysis of fast biological processes. Herein, we describe the development of a method in which the formation of a parallel coiled coil triggers the transfer of a fluorescence dye from a thioester-linked coil peptide conjugate onto a cysteine-modified coil peptide. This labeling method requires only small tag sequences (max 23 aa) and occurs with high tag specificity. We show that size matching of the coil peptides and a suitable thioester reactivity allow the acyl transfer reaction to proceed within minutes (rather than hours). We demonstrate the versatility of this method by applying it to the labeling of different G-protein coupled membrane receptors including the human neuropeptide Y receptors 1, 2, 4, 5, the neuropeptide FF receptors 1 and 2, and the dopamine receptor 1. The labeled receptors are fully functional and able to bind the respective ligand with high affinity. Activity is not impaired as demonstrated by activation, internalization, and recycling experiments.
Journal Article Research Support, Non-U.S. Gov't United States
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. Institut fur Biochemie, Universitat Leipzig , Bruderstrasse 34, D-04103 Leipzig, Germany. Institut fur Biochemie, Universitat Leipzig , Bruderstrasse 34, D-04103 Leipzig, Germany. Institut fur Biochemie, Universitat Leipzig , Bruderstrasse 34, D-04103 Leipzig, Germany. Institut fur Chemie, Humboldt-Universitat zu Berlin , Brook-Taylor-Strasse 2, D-12489 Berlin, Germany. alt-title: Bioconjugate chemistry number: 10 accession-num: 26367072
Keywords: Humans; Protein Conformation; Cysteine/chemistry; Solid-Phase Synthesis Techniques; Fluoresceins/chemistry; Fluorescent Dyes/*chemistry; HEK293 Cells; Membrane Proteins/*chemistry/metabolism; Peptides/chemical synthesis/chemistry; Pyrazines/chemistry; Receptors, Neuropeptide Y/chemistry/metabolism; Receptors, Neuropeptide/chemistry/metabolism; Rhodamines/chemistry

Native chemical ligation between asparagine and valine: application and limitations for the synthesis of tri-phosphorylated C-terminal tau - Reimann, O.; Glanz, M.; Hackenberger, C. P. (Bioorg. Med. Chem., 2015)
We present the successful native chemical ligation (NCL) at an Asn-Val site employing beta-mercaptovaline and subsequent desulfurization in the synthesis of native phosphorylated C-terminal tau, relevant for Alzheimer's disease related research. Despite recent progress in the field of NCL we illustrate limitations of this ligation site that stem from thioester hydrolysis and predominantly aspartimide formation. We systematically investigated the influence of pH, temperature, peptide concentration and thiol additives on the outcome of this ligation and identified conditions under which the ligation can be driven toward complete conversion, which required the deployment of a high surplus of thioester. Application of the optimized conditions allowed us to gain access to challenging tri-phosphorylated C-terminal tau peptide in practical yields.
Journal Article Research Support, Non-U.S. Gov't England
The following values have no corresponding Zotero field: auth-address: Leibniz-Institut fur Molekulare Pharmakologie (FMP), Robert-Rossle-Strasse 10, 13125 Berlin, Germany; Freie Universitat Berlin, Institut fur Chemie und Biochemie, Takustrasse 3, 14195 Berlin, Germany. Leibniz-Institut fur Molekulare Pharmakologie (FMP), Robert-Rossle-Strasse 10, 13125 Berlin, Germany; Humboldt Universitat zu Berlin, Department Chemie, Brook-Taylor-Strasse 2, 12489 Berlin, Germany. Leibniz-Institut fur Molekulare Pharmakologie (FMP), Robert-Rossle-Strasse 10, 13125 Berlin, Germany; Humboldt Universitat zu Berlin, Department Chemie, Brook-Taylor-Strasse 2, 12489 Berlin, Germany. Electronic address: hackenbe@fmp-berlin.de. alt-title: Bioorganic & medicinal chemistry number: 12 accession-num: 25882528
Keywords: Amino Acid Sequence; Molecular Sequence Data; Phosphorylation; Asparagine/*chemistry; Penicillamine/chemistry; Sulfur/chemistry; tau Proteins/*chemical synthesis/chemistry; Valine/*chemistry

Chemical synthesis of proteins with non-strategically placed cysteines using selenazolidine and selective deselenization - Reddy, P. S.; Dery, S.; Metanis, N. (Angew. Chem. Int. Ed., 2015)
Although native chemical ligation has enabled the synthesis of hundreds of proteins, not all proteins are accessible through typical ligation conditions. The challenging protein, 125-residue human phosphohistidine phosphatase 1 (PHPT1), has three cysteines near the C-terminus, which are not strategically placed for ligation. Herein, we report the first sequential native chemical ligation/deselenization reaction. PHPT1 was prepared from three unprotected peptide segments using two ligation reactions at cysteine and alanine junctions. Selenazolidine was utilized as a masked precursor for N-terminal selenocysteine in the middle segment, and, following ligation, deselenization provided the native alanine residue. This approach was used to synthesize both the wild-type PHPT1 and an analogue in which the active-site histidine was substituted with the unnatural and isosteric amino acid beta-thienyl-l-alanine. The activity of both proteins was studied and compared, providing insights into the enzyme active site.
Journal Article Research Support, Non-U.S. Gov't Germany
The following values have no corresponding Zotero field: auth-address: The Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra, Givat Ram, Jerusalem, 91904, Israel. The Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra, Givat Ram, Jerusalem, 91904, Israel. The Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra, Givat Ram, Jerusalem, 91904, Israel. Metanis@mail.huji.ac.il. alt-title: Angewandte Chemie (International ed number: 3 accession-num: 26636774
Keywords: Proteins/*chemical synthesis/chemistry; Cysteine/*chemistry; Chromatography, High Pressure Liquid; Hydrogen Bonding; Selenium/*chemistry

Aldehyde capture ligation for synthesis of native peptide bonds - Raj, Monika; Wu, Huabin; Blosser, Sarah L.; Vittoria, Marc A.; Arora, Paramjit S. (J. Am. Chem. Soc., 2015)
doi: 10.1021/jacs.5b03538 0002-7863 doi: 10.1021/jacs.5b03538
The following values have no corresponding Zotero field: number: 21 publisher: American Chemical Society

Solid phase protein chemical synthesis - Raibaut, L.; El Mahdi, O.; Melnyk, O. (Top. Curr. Chem., 2015)
The chemical synthesis of peptides or small proteins is often an important step in many research projects and has stimulated the development of numerous chemical methodologies. The aim of this review is to give a substantial overview of the solid phase methods developed for the production or purification of polypeptides. The solid phase peptide synthesis (SPPS) technique has facilitated considerably the access to short peptides (<50 amino acids). However, its limitations for producing large homogeneous peptides have stimulated the development of solid phase covalent or non-covalent capture purification methods. The power of the native chemical ligation (NCL) reaction for protein synthesis in aqueous solution has also been adapted to the solid phase by the combination of novel linker technologies, cysteine protection strategies and thioester or N,S-acyl shift thioester surrogate chemistries. This review details pioneering studies and the most recent publications related to the solid phase chemical synthesis of large peptides and proteins.
Journal Article Germany
The following values have no corresponding Zotero field: auth-address: Institut Pasteur de Lille, UMR CNRS 8161, Universite de Lille, 59021, Lille, France. alt-title: Topics in current chemistry accession-num: 25791484

Selectively activatable latent thiol and selenolesters simplify the access to cyclic or branched peptide scaffolds - Raibaut, L.; Drobecq, H.; Melnyk, O. (Org. Lett., 2015)
The cyclic dichalcogenides based on the bis(2-chalcogenoethyl)amide structure are latent N,S (SEA, chalcogen = S) or N,Se (SeEA, chalcogen = Se) acyl shift systems. The large difference in the reducing potential between SEA and SeEA dichalcogenides allows their sequential and selective activation by reduction. Based on these concepts, one-pot three or four peptide segment assembly processes were designed, facilitating access to branched or cyclic peptide scaffolds.
Cited By :15
Cited By :15
Export Date: 25 May 2018
Export Date: 25 May 2018
Journal Article United States

An oxazetidine amino acid for chemical protein synthesis by rapid, serine-forming ligations - Pusterla, I.; Bode, J. W. (Nat. Chem., 2015)
Amide-forming ligation reactions allow the chemical synthesis of proteins by the union of unprotected peptide segments, and enable the preparation of protein derivatives not accessible by expression or bioengineering approaches. The native chemical ligation (NCL) of thioesters and N-terminal cysteines is unquestionably the most successful approach, but is not ideal for all synthetic targets. Here we describe the synthesis of an Fmoc-protected oxazetidine amino acid for use in the alpha-ketoacid-hydroxylamine (KAHA) amide ligation. When incorporated at the N-terminus of a peptide segment, this four-membered cyclic hydroxylamine can be used for rapid serine-forming ligations with peptide alpha-ketoacids. This ligation operates at low concentration (100 muM-5 mM) and mild temperatures (20-25 degrees C). The utility of the reaction was demonstrated by the synthesis of S100A4, a 12 kDa calcium-binding protein not easily accessible by NCL or other amide-forming reactions due to its primary sequence and properties.
Journal Article Research Support, Non-U.S. Gov't England
The following values have no corresponding Zotero field: auth-address: Department of Chemistry and Applied Biosciences, Laboratorium fur Organische Chemie, Vladimir Prelog Weg 3, ETH Zurich, Zurich 8093, Switzerland. 1] Department of Chemistry and Applied Biosciences, Laboratorium fur Organische Chemie, Vladimir Prelog Weg 3, ETH Zurich, Zurich 8093, Switzerland [2] Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Chikusa, Nagoya 464-8602, Japan. alt-title: Nature chemistry number: 8 accession-num: 26201744
Keywords: Amino Acid Sequence; Proteins/*chemical synthesis; Amino Acids/chemistry; Fluorenes/chemistry; Hydroxylamine/*chemistry; Serine/*chemistry

The basics of thiols and cysteines in redox biology and chemistry - Poole, L. B. (Free Radic. Biol. Med., 2015)
Cysteine is one of the least abundant amino acids, yet it is frequently found as a highly conserved residue within functional (regulatory, catalytic, or binding) sites in proteins. It is the unique chemistry of the thiol or thiolate group of cysteine that imparts to functional sites their specialized properties (e.g., nucleophilicity, high-affinity metal binding, and/or ability to form disulfide bonds). Highlighted in this review are some of the basic biophysical and biochemical properties of cysteine groups and the equations that apply to them, particularly with respect to pKa and redox potential. Also summarized are the types of low-molecular-weight thiols present in high concentrations in most cells, as well as the ways in which modifications of cysteinyl residues can impart or regulate molecular functions important to cellular processes, including signal transduction.
Poole, Leslie B R01 GM050389/GM/NIGMS NIH HHS/ R33 CA177461/CA/NCI NIH HHS/ R01GM050389/GM/NIGMS NIH HHS/ R33CA177461/CA/NCI NIH HHS/ Free Radic Biol Med. 2015 Mar;80:148-57. doi: 10.1016/j.freeradbiomed.2014.11.013. Epub 2014 Nov 27.
The following values have no corresponding Zotero field: auth-address: Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA. Electronic address: lbpoole@wakehealth.edu. alt-title: Free radical biology & medicine edition: 2014/11/30 accession-num: 25433365 work-type: Research Support, N.I.H., Extramural Review
Keywords: Animals; Humans; Kinetics; *Electrons; *Signal Transduction; Biocatalysis; Cysteine/*chemistry/metabolism; Disulfides/chemistry/metabolism; Free Radicals/*chemistry/metabolism; Glutathione/chemistry/metabolism; Oxidation-Reduction; Oxidoreductases/chemistry/metabolism; Sulfhydryl Compounds/*chemistry/metabolism; Thermodynamics

Efficient photochemical synthesis of peptide-α-phenylthioesters - Pardo, Andrew; Hogenauer, Tyrone J.; Cai, Zhefeng; Vellucci, Julian A.; Castillo, Efrain M.; Dirk, Carl W.; Franz, Andreas H.; Michael, Katja (ChemBioChem, 2015)
Low yields and substantial epimerization of peptide-α-thioesters often compromise the overall efficiency of native chemical ligation (NCL). Peptide arylthioesters are more reactive than peptide alkylthioesters in NCL, but are also more difficult to handle due to their propensity to hydrolyze, and are therefore often generated in situ. However, pre-prepared peptide arylthioesters are required for some NCL applications. Here we present a 7-nitroindoline-based photochemical method that generates protected peptide phenylthioesters under neutral reaction conditions via their activated esters from photoreactive peptide precursors in high isolated yields, and with low levels of epimerization. This method is fully compatible with Fmoc-strategy solid-phase peptide synthesis. Global deprotection with trifluoroacetic acid furnishes peptide phenylthioesters for NCL. Photoreactive peptide precursors can also be converted into their hydrazides in two steps by this method.
The following values have no corresponding Zotero field: number: 13 publisher: WILEY-VCH Verlag
Keywords: peptides; photochemistry; acylation; hydrazides; thioesters

Correction: Comparison of the reactivity of b-thiolactones and b-lactones toward ring-opening by thiols and amines - Noel, Amandine; Delpech, Bernard; Crich, David (Org. Biomol. Chem., 2015)
Correction for 'Comparison of the reactivity of [small beta]-thiolactones and [small beta]-lactones toward ring-opening by thiols and amines' by Amandine Noel et al., Org. Biomol. Chem., 2012, 10, 6480-6483.
1477-0520 10.1039/C5OB90143J
The following values have no corresponding Zotero field: number: 35 publisher: The Royal Society of Chemistry

Rapid additive-free selenocystine-selenoester peptide ligation - Mitchell, N. J.; Malins, L. R.; Liu, X.; Thompson, R. E.; Chan, B.; Radom, L.; Payne, R. J. (J. Am. Chem. Soc., 2015)
We describe an unprecedented reaction between peptide selenoesters and peptide dimers bearing N-terminal selenocystine that proceeds in aqueous buffer to afford native amide bonds without the use of additives. The selenocystine-selenoester ligations are complete in minutes, even at sterically hindered junctions, and can be used in concert with one-pot deselenization chemistry. Various pathways for the transformation are proposed and probed through a combination of experimental and computational studies. Our new reaction manifold is also showcased in the total synthesis of two proteins.
Journal Article United States
The following values have no corresponding Zotero field: auth-address: School of Chemistry, The University of Sydney , Sydney, NSW 2006, Australia. School of Chemistry, The University of Sydney , Sydney, NSW 2006, Australia. School of Chemistry, The University of Sydney , Sydney, NSW 2006, Australia. School of Chemistry, The University of Sydney , Sydney, NSW 2006, Australia. School of Chemistry, The University of Sydney , Sydney, NSW 2006, Australia. School of Chemistry, The University of Sydney , Sydney, NSW 2006, Australia. School of Chemistry, The University of Sydney , Sydney, NSW 2006, Australia. alt-title: Journal of the American Chemical Society number: 44 accession-num: 26487084

A mechanistic study of thioester hydrolysis with heavy atom kinetic isotope effects - Marlier, John F.; Fogle, Emily J.; Redman, Richard L.; Stillman, Anthony D.; Denison, Matthew A.; Robins, Lori I. (J. Org. Chem., 2015)
doi: 10.1021/jo502472m 0022-3263 doi: 10.1021/jo502472m
The following values have no corresponding Zotero field: number: 3 publisher: American Chemical Society

Recent extensions to native chemical ligation for the chemical synthesis of peptides and proteins - Malins, L. R.; Payne, R. J. (Curr. Opin. Chem. Biol., 2015)
Native chemical ligation continues to play a pivotal role in the synthesis of increasingly complex peptide and protein targets twenty years after its initial report. This opinion article will highlight a number of recent, powerful extensions of the technology that have expanded the scope of the reaction, accelerated ligation rates, enabled chemoselective post-ligation modifications, and streamlined the ligation of multiple peptide fragments. These advances have facilitated the synthesis of a number of impressive protein targets to date and hold great promise for the continued application of native chemical ligation for the detailed study of protein structure and function.
Journal Article Research Support, Non-U.S. Gov't Review England
The following values have no corresponding Zotero field: auth-address: School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia. School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: richard.payne@sydney.edu.au. alt-title: Current opinion in chemical biology accession-num: 25285753
Keywords: Models, Molecular; Proteins/*chemical synthesis/chemistry; Peptides/*chemical synthesis/chemistry; Acylation; Sulfhydryl Compounds/chemical synthesis/chemistry; Sulfur/chemistry; Amino Acids/chemical synthesis/chemistry; Selenium Compounds/chemical synthesis/chemistry

Oxidative deselenization of selenocysteine: applications for programmed ligation at serine - Malins, L. R.; Mitchell, N. J.; McGowan, S.; Payne, R. J. (Angew. Chem. Int. Ed., 2015)
Despite the unique chemical properties of selenocysteine (Sec), ligation at Sec is an under-utilized methodology for protein synthesis. We describe herein an unprecedented protocol for the conversion of Sec to serine (Ser) in a single, high-yielding step. When coupled with ligation at Sec, this transformation provides a new approach to programmed ligations at Ser residues. This new reaction is compatible with a wide range of functionality, including the presence of unprotected amino acid side chains and appended glycans. The utility of the methodology is demonstrated in the rapid synthesis of complex glycopeptide fragments of the epithelial glycoproteins MUC5AC and MUC4 and through the total synthesis of the structured, cysteine (Cys)-free protein eglin C.
Journal Article Research Support, Non-U.S. Gov't Germany
The following values have no corresponding Zotero field: auth-address: School of Chemistry, The University of Sydney, NSW 2006 (Australia) http://sydney.edu.au/science/chemistry/ approximately payne/index.html. School of Chemistry, The University of Sydney, NSW 2006 (Australia) http://sydney.edu.au/science/chemistry/ approximately payne/index.html. Department of Biochemistry and Molecular Biology, Monash University, Melbourne, VIC 3800 (Australia). School of Chemistry, The University of Sydney, NSW 2006 (Australia) http://sydney.edu.au/science/chemistry/ approximately payne/index.html. richard.payne@sydney.edu.au. alt-title: Angewandte Chemie (International ed number: 43 accession-num: 26384718

Synthesis of b-thiol phenylalanine for applications in one-pot ligation-desulfurization chemistry - Malins, L. R.; Giltrap, A. M.; Dowman, L. J.; Payne, R. J. (Org. Lett., 2015)
The efficient synthesis of a beta-thiol phenylalanine derivative is described starting from Garner's aldehyde. The utility of this amino acid in peptide ligation-desulfurization chemistry is described, including the trifluoroethanethiol (TFET)-promoted one-pot assembly of the 62 residue peptide hormone augurin.
Journal Article Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: School of Chemistry, The University of Sydney, New South Wales, 2006, Australia. School of Chemistry, The University of Sydney, New South Wales, 2006, Australia. School of Chemistry, The University of Sydney, New South Wales, 2006, Australia. School of Chemistry, The University of Sydney, New South Wales, 2006, Australia. alt-title: Organic letters number: 9 accession-num: 25860301
Keywords: Molecular Structure; Ligation; Aldehydes/chemistry; Neoplasm Proteins/chemistry; Peptide Hormones/chemistry; Peptides/chemistry; Phenylalanine/*analogs & derivatives/*chemical synthesis/chemistry; Sulfhydryl Compounds/*chemical synthesis/chemistry; Trifluoroethanol/analogs & derivatives/chemistry

A new strategy for synthesis of branched cyclic peptide by Asn side-chain hydrazide ligation - Lu, Jian; Tian, Xiao-Bo; Huang, Wei (Chinese Chem. Lett., 2015)
Abstract Here, we report a new strategy for rapid synthesis of branched peptide by side-chain hydrazide ligation at Asn. The hydrazide was converted to thioester at Asn side chain by NaNO2 and thiol reagent, and sequential ligation with an N-terminus Cys-peptide efficiently afforded the branched peptide. A branched cyclic peptide was successfully synthesized by side-chain ligation with a two-Cys-peptide and formation of a disulfide bond. This approach provides a new way for expeditious synthesis of branched peptides and facilitates the design of neopeptides as functional bio-mimics.
1001-8417
The following values have no corresponding Zotero field: number: 8
Keywords: Asn side-chain ligation; Branched cyclic peptide; Hydrazide ligation; Neopeptide

A type of auxiliary for native chemical peptide ligation beyond cysteine and glycine Junctions - Loibl, S. F.; Harpaz, Z.; Seitz, O. (Angew. Chem. Int. Ed., 2015)
Native chemical ligation enables the chemical synthesis of proteins. Previously, thiol-containing auxiliary groups have been used to extend the reaction scope beyond N-terminal cysteine residues. However, the N-benzyl-type auxiliaries used so far result in rather low reaction rates. Herein, a new N(alpha) -auxiliary is presented. Consideration of a radical fragmentation for cleavage led to the design of a new auxiliary group which is selectively removed under mildly basic conditions (pH 8.5) in the presence of TCEP and morpholine. Most importantly and in contrast to previously described auxiliaries, the 2-mercapto-2-phenethyl auxiliary is not limited to Gly-containing sites and ligations succeed at sterically demanding junctions. The auxiliary is introduced in high yield by on-resin reductive amination with commercially available amino acid building blocks. The synthetic utility of the method is demonstrated by the synthesis of two antimicrobial proteins, DCD-1L and opistoporin-2.
Journal Article Research Support, Non-U.S. Gov't Germany
The following values have no corresponding Zotero field: auth-address: Institut fur Chemie, Humboldt-Universitat zu Berlin, Brook-Taylor-Strasse 2, 12489 Berlin (Germany). Institut fur Chemie, Humboldt-Universitat zu Berlin, Brook-Taylor-Strasse 2, 12489 Berlin (Germany). Institut fur Chemie, Humboldt-Universitat zu Berlin, Brook-Taylor-Strasse 2, 12489 Berlin (Germany). oliver.seitz@chemie.hu-berlin.de. alt-title: Angewandte Chemie (International ed number: 50 accession-num: 26545341

Convergent chemical synthesis of [lysine(24,38,83)] human erythropoietin - Liu, S.; Pentelute, B. L.; Kent, S. B. H. (Angew. Chem. Int. Ed., 2015)
R01 GM075993/GM/NIGMS NIH HHS/United States R01 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. Germany
The following values have no corresponding Zotero field: auth-address: Department of Biochemistry and Molecular Biology, Gordon Center for Integrative Science, The University of Chicago, 929 East 57th Street, Chicago, IL 60637, USA. alt-title: Angewandte Chemie (International ed number: 4 accession-num: 22180156
Keywords: Humans; Cell Line; Solid-Phase Synthesis Techniques; Peptides/chemical synthesis/chemistry; Amino Acid Substitution; Circular Dichroism; Erythropoietin/analogs & derivatives/*chemical synthesis/metabolism; Protein Folding

Topics in Current Chemistry. Protein Ligation and Total Synthesis - Liu, L. (Springer International Publishing, 2015)
Keywords: #nosource

Chemical ligation of the influenza M2 protein for solid-state NMR characterization of the cytoplasmic domain - Kwon, Byungsu; Tietze, Daniel; White, Paul B.; Liao, Shu Y.; Hong, Mei (Protein Sci., 2015)
Solid-state NMR-based structure determination of membrane proteins and large protein complexes faces the challenge of limited spectral resolution when the proteins are uniformly 13C-labeled. A strategy to meet this challenge is chemical ligation combined with site-specific or segmental labeling. While chemical ligation has been adopted in NMR studies of water-soluble proteins, it has not been demonstrated for membrane proteins. Here we show chemical ligation of the influenza M2 protein, which contains a transmembrane (TM) domain and two extra-membrane domains. The cytoplasmic domain, which contains an amphipathic helix (AH) and a cytoplasmic tail, is important for regulating virus assembly, virus budding, and the proton channel activity. A recent study of uniformly 13C-labeled full-length M2 by spectral simulation suggested that the cytoplasmic tail is unstructured. To further test this hypothesis, we conducted native chemical ligation of the TM segment and part of the cytoplasmic domain. Solid-phase peptide synthesis of the two segments allowed several residues to be labeled in each segment. The post-AH cytoplasmic residues exhibit random-coil chemical shifts, low bond order parameters, and a surface-bound location, thus indicating that this domain is a dynamic random coil on the membrane surface. Interestingly, the protein spectra are similar between a model membrane and a virus-mimetic membrane, indicating that the structure and dynamics of the post-AH segment is insensitive to the lipid composition. This chemical ligation approach is generally applicable to medium-sized membrane proteins to provide site-specific structural constraints, which complement the information obtained from uniformly 13C, 15N-labeled proteins.
1469-896X
The following values have no corresponding Zotero field: number: 7
Keywords: chemical ligation; intrinsically disordered proteins; random coil; total protein synthesis

Serine and Cysteine pi-Interactions in Nature: A Comparison of the Frequency, Structure, and Stability of Contacts Involving Oxygen and Sulfur - Hussain, Hanzala B.; Wilson, Katie A.; Wetmore, Stacey D. (Aust. J. Chem., 2015)
Despite many DNA–protein π-interactions in high-resolution crystal structures, only four X–H···π or X···π interactions were found between serine (Ser) or cysteine (Cys) and DNA nucleobase π-systems in over 100 DNA–protein complexes (where X = O for Ser and X = S for Cys). Nevertheless, 126 non-covalent contacts occur between Ser or Cys and the aromatic amino acids in many binding arrangements within proteins. Furthermore, Ser and Cys protein–protein π-interactions occur with similar frequencies and strengths. Most importantly, due to the great stability that can be provided to biological macromolecules (up to –20 kJ mol–1 for neutral π-systems or –40 kJ mol–1 for cationic π-systems), Ser and Cys π-interactions should be considered when analyzing protein stability and function.
The following values have no corresponding Zotero field: number: 3

Chemical and biological tools for the preparation of modified histone proteins - Howard, C. J.; Yu, R. R.; Gardner, M. L.; Shimko, J. C.; Ottesen, J. J. (Top. Curr. Chem., 2015)
Eukaryotic chromatin is a complex and dynamic system in which the DNA double helix is organized and protected by interactions with histone proteins. This system is regulated through a large network of dynamic post-translational modifications (PTMs) which ensure proper gene transcription, DNA repair, and other processes involving DNA. Homogenous protein samples with precisely characterized modification sites are necessary to understand better the functions of modified histone proteins. Here, we discuss sets of chemical and biological tools developed for the preparation of modified histones, with a focus on the appropriate choice of tool for a given target. We start with genetic approaches for the creation of modified histones, including the incorporation of genetic mimics of histone modifications, chemical installation of modification analogs, and the use of the expanded genetic code to incorporate modified amino acids. We also cover the chemical ligation techniques which have been invaluable in the generation of complex modified histones indistinguishable from their natural counterparts. We end with a prospectus on future directions.
R01 GM083055/GM/NIGMS NIH HHS/United States Journal Article Germany
The following values have no corresponding Zotero field: auth-address: Department of Chemistry and Biochemistry and The Ohio State Biochemistry Program, The Ohio State University, Columbus, OH, 43210, USA. alt-title: Topics in current chemistry accession-num: 25863817
Keywords: Models, Molecular; Protein Conformation; Histones/*chemical synthesis/*chemistry; Chemistry Techniques, Synthetic/*methods; Chromatin/chemistry/metabolism; Eukaryota; Gene Expression Regulation; Protein Engineering/*methods

Organic compounds on comet 67P/Churyumov-Gerasimenko revealed by COSAC mass spectrometry - Goesmann, Fred; Rosenbauer, Helmut; Bredehöft, Jan Hendrik; Cabane, Michel; Ehrenfreund, Pascale; Gautier, Thomas; Giri, Chaitanya; Krüger, Harald; Le Roy, Léna; MacDermott, Alexandra J.; McKenna-Lawlor, Susan; Meierhenrich, Uwe J.; et al. (Science, 2015)
Comets harbor the most pristine material in our solar system in the form of ice, dust, silicates, and refractory organic material with some interstellar heritage. The evolved gas analyzer Cometary Sampling and Composition (COSAC) experiment aboard Rosetta’s Philae lander was designed for in situ analysis of organic molecules on comet 67P/Churyumov-Gerasimenko. Twenty-five minutes after Philae’s initial comet touchdown, the COSAC mass spectrometer took a spectrum in sniffing mode, which displayed a suite of 16 organic compounds, including many nitrogen-bearing species but no sulfur-bearing species, and four compounds—methyl isocyanate, acetone, propionaldehyde, and acetamide—that had not previously been reported in comets.%U http://science.sciencemag.org/content/sci/349/6247/aab0689.full.pdf
The following values have no corresponding Zotero field: number: 6247
Keywords: #nosource

Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013 - Global Burden of Disease Study, Collaborators (Lancet, 2015)
BACKGROUND: Up-to-date evidence about levels and trends in disease and injury incidence, prevalence, and years lived with disability (YLDs) is an essential input into global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013), we estimated these quantities for acute and chronic diseases and injuries for 188 countries between 1990 and 2013. METHODS: Estimates were calculated for disease and injury incidence, prevalence, and YLDs using GBD 2010 methods with some important refinements. Results for incidence of acute disorders and prevalence of chronic disorders are new additions to the analysis. Key improvements include expansion to the cause and sequelae list, updated systematic reviews, use of detailed injury codes, improvements to the Bayesian meta-regression method (DisMod-MR), and use of severity splits for various causes. An index of data representativeness, showing data availability, was calculated for each cause and impairment during three periods globally and at the country level for 2013. In total, 35 620 distinct sources of data were used and documented to calculated estimates for 301 diseases and injuries and 2337 sequelae. The comorbidity simulation provides estimates for the number of sequelae, concurrently, by individuals by country, year, age, and sex. Disability weights were updated with the addition of new population-based survey data from four countries. FINDINGS: Disease and injury were highly prevalent; only a small fraction of individuals had no sequelae. Comorbidity rose substantially with age and in absolute terms from 1990 to 2013. Incidence of acute sequelae were predominantly infectious diseases and short-term injuries, with over 2 billion cases of upper respiratory infections and diarrhoeal disease episodes in 2013, with the notable exception of tooth pain due to permanent caries with more than 200 million incident cases in 2013. Conversely, leading chronic sequelae were largely attributable to non-communicable diseases, with prevalence estimates for asymptomatic permanent caries and tension-type headache of 2·4 billion and 1·6 billion, respectively. The distribution of the number of sequelae in populations varied widely across regions, with an expected relation between age and disease prevalence. YLDs for both sexes increased from 537·6 million in 1990 to 764·8 million in 2013 due to population growth and ageing, whereas the age-standardised rate decreased little from 114·87 per 1000 people to 110·31 per 1000 people between 1990 and 2013. Leading causes of YLDs included low back pain and major depressive disorder among the top ten causes of YLDs in every country. YLD rates per person, by major cause groups, indicated the main drivers of increases were due to musculoskeletal, mental, and substance use disorders, neurological disorders, and chronic respiratory diseases; however HIV/AIDS was a notable driver of increasing YLDs in sub-Saharan Africa. Also, the proportion of disability-adjusted life years due to YLDs increased globally from 21·1% in 1990 to 31·2% in 2013. INTERPRETATION: Ageing of the world’s population is leading to a substantial increase in the numbers of individuals with sequelae of diseases and injuries. Rates of YLDs are declining much more slowly than mortality rates. The non-fatal dimensions of disease and injury will require more and more attention from health systems. The transition to non-fatal outcomes as the dominant source of burden of disease is occurring rapidly outside of sub-Saharan Africa. Our results can guide future health initiatives through examination of epidemiological trends and a better understanding of variation across countries.
26063472[pmid] Lancet
The following values have no corresponding Zotero field: number: 9995 accession-num: PMC4561509

Combining triazole ligation and enzymatic glycosylation on solid phase simplifies the synthesis of very long glycoprotein analogues - Galibert, Mathieu; Piller, Veronique; Piller, Friedrich; Aucagne, Vincent; Delmas, Agnes F. (Chem. Sci., 2015)
The solid-phase chemical assembly of a protein through iterative chemoselective ligation of unprotected peptide segments can be followed with chemical and/or enzymatic transformations of the resulting immobilized protein, the latter steps thus benefitting from the advantages provided by the solid support. We demonstrate here the usefulness of this strategy for the chemo-enzymatic synthesis of glycoprotein analogues. A linker was specifically designed for application to the synthesis of O-glycoproteins: this new linker is readily cleaved under mild aqueous conditions compatible with very sensitive glycosidic bonds, but is remarkably stable under a wide range of chemical and biochemical conditions. It was utilized for solid-supported N-to-C peptidomimetic triazole ligation followed by enzymatic glycosylation, ultimately leading to a very large MUC1-derived glycoprotein containing 160 amino acid residues, 24 [small alpha]-GalNAc moieties linked to Ser and Thr, and 3 triazoles as peptide bond mimetics.
2041-6520 10.1039/C5SC00773A
The following values have no corresponding Zotero field: number: 6 publisher: The Royal Society of Chemistry

SUMOylation-mediated regulation of cell cycle progression and cancer - Eifler, K.; Vertegaal, A. C. (Trends Biochem. Sci., 2015)
Protein conjugation with Small ubiquitin-like modifier (SUMOylation) has critical roles during cell cycle progression. Many important cell cycle regulators, including many oncogenes and tumor suppressors, are functionally regulated via SUMOylation. The dynamic SUMOylation pattern observed throughout the cell cycle is ensured via distinct spatial and temporal regulation of the SUMO machinery. Additionally, SUMOylation cooperates with other post-translational modifications to mediate cell cycle progression. Deregulation of these SUMOylation and deSUMOylation enzymes causes severe defects in cell proliferation and genome stability. Different types of cancer were recently shown to be dependent on a functioning SUMOylation system, a finding that could be exploited in anticancer therapies.
310913/European Research Council/International Journal Article Research Support, Non-U.S. Gov't Review England
The following values have no corresponding Zotero field: auth-address: Department of Molecular Cell Biology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. Electronic address: k.eifler@lumc.nl. Department of Molecular Cell Biology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. Electronic address: vertegaal@lumc.nl. alt-title: Trends in biochemical sciences number: 12 accession-num: 26601932

Synthesis of unprotected linear or cyclic O-acyl isopeptides in water using bis(2-sulfanylethyl)amido peptide ligation - Desmet, R.; Pauzuolis, M.; Boll, E.; Drobecq, H.; Raibaut, L.; Melnyk, O. (Org. Lett., 2015)
SEA ligation proceeds chemoselectively at pH 3, i.e., at a pH where the O-acyl isopeptides are protected by protonation. This property was used for synthesizing unprotected O-acyl isopeptides in water, starting from peptide segments which are easily accessible by the Fmoc SPPS.
Journal article
The following values have no corresponding Zotero field: auth-address: UMR CNRS 8161, Universite Lille, Pasteur Institute of Lille 59021 Lille, France. UMR CNRS 8161, Universite Lille, Pasteur Institute of Lille 59021 Lille, France. UMR CNRS 8161, Universite Lille, Pasteur Institute of Lille 59021 Lille, France. UMR CNRS 8161, Universite Lille, Pasteur Institute of Lille 59021 Lille, France. UMR CNRS 8161, Universite Lille, Pasteur Institute of Lille 59021 Lille, France. UMR CNRS 8161, Universite Lille, Pasteur Institute of Lille 59021 Lille, France. alt-title: Organic letters number: 13 accession-num: 26075704

Computational study and kinetic analysis of the aminolysis of thiolactones - Desmet, Gilles B.; D'hooge, Dagmar R.; Sabbe, Maarten K.; Marin, Guy B.; Du Prez, Filip E.; Espeel, Pieter; Reyniers, Marie-Françoise (J. Org. Chem., 2015)
doi: 10.1021/acs.joc.5b01446 0022-3263 doi: 10.1021/acs.joc.5b01446
The following values have no corresponding Zotero field: number: 17 publisher: American Chemical Society

Insights into the deselenization of selenocysteine into alanine and serine - Dery, Shahar; Reddy, Post Sai; Dery, Linoy; Mousa, Reem; Dardashti, Rebecca Notis; Metanis, Norman (Chem. Sci., 2015)
The development of native chemical ligation coupled with desulfurization has allowed ligation at several new ligation junctions. However, desulfurization also converts all cysteine residues in the protein sequence into alanine. Deselenization of selenocysteine, in contrast, selectively removes the selenol group to give alanine in the presence of unprotected cysteines. In this study we shed more light onto the deselenization mechanism of selenocysteine to alanine and provide optimized conditions for the reaction. The deselenization can be accomplished in one minute under anaerobic conditions to give alanine. Under aerobic conditions (oxygen saturation), selenocysteine is converted into serine.
2041-6520 10.1039/C5SC02528A
The following values have no corresponding Zotero field: number: 11 publisher: The Royal Society of Chemistry

Vibrational spectroscopy and conformation of S-ethyl thioacetate: CH3COSCH2CH3 and comparison with C(O)S and C(O)O compounds - Defonsi Lestard, MarÃa Eliana; Tuttolomondo, MarÃa Eugenia; Ben Altabef, Aida (Spectrochim. Acta Part A: Mol. Biomol. Spectrosc., 2015)
Abstract The molecular structure and conformational properties of S-ethyl thioacetate, CH3COSCH2CH3, were determined in the gas phase by electron diffraction and vibrational spectroscopy (IR and Raman). The experimental investigations were supplemented by ab initio (MP2) and DFT quantum chemical calculations at different levels of theory. Theoretical methods reveal two structures with Cs (anti, anti) and C1 (anti, gauche) symmetries. The infrared and Raman spectra for different phases were also recorded and the bands observed assigned to the vibrational normal modes. Liquid Raman and infrared spectra in liquid and gaseous state measurements revealed the presence of two conformations anti, anti (Cs symmetry) and anti, gauche (C1 symmetry). The study was completed using natural bond orbital (NBO) analysis. We have also analyzed the internal rotation barrier about the C(O)SCC dihedral angle using a variety of computational approaches and natural bond orbital (NBO) analyses to understand the nature of the potential function and to explain the preferred conformation of the molecule.
1386-1425
Keywords: C(O)S and C(O)O compounds; Infrared; Raman; S-ethyl thioacetate

Examination of mercaptobenzyl sulfonates as catalysts for native chemical ligation: application to the assembly of a glycosylated Glucagon-Like Peptide 1 (GLP-1) analogue - Cowper, Ben; Sze, Tsz Mei; Premdjee, Bhavesh; Bongat White, Aileen F.; Hacking, Andrew; Macmillan, Derek (Chem. Commun., 2015)
3/4-Mercaptobenzyl sulfonates were investigated as aryl thiol catalysts for native chemical ligation (NCL). Whilst catalysing NCL processes at a similar rate to 4-mercaptophenyl acetic acid (MPAA), the increased polarity and solubility of 3-mercaptobenzyl sulfonate in particular may favour its selection as NCL catalyst in many instances.
1359-7345 10.1039/C4CC09502B
The following values have no corresponding Zotero field: number: 15 publisher: The Royal Society of Chemistry

Spontaneous reconstitution of functional transmembrane proteins during bioorthogonal phospholipid membrane synthesis - Cole, C. M.; Brea, R. J.; Kim, Y. H.; Hardy, M. D.; Yang, J.; Devaraj, N. K. (Angew. Chem. Int. Ed., 2015)
Transmembrane proteins are critical for signaling, transport, and metabolism, yet their reconstitution in synthetic membranes is often challenging. Non-enzymatic and chemoselective methods to generate phospholipid membranes in situ would be powerful tools for the incorporation of membrane proteins. Herein, the spontaneous reconstitution of functional integral membrane proteins during the de novo synthesis of biomimetic phospholipid bilayers is described. The approach takes advantage of bioorthogonal coupling reactions to generate proteoliposomes from micelle-solubilized proteins. This method was successfully used to reconstitute three different transmembrane proteins into synthetic membranes. This is the first example of the use of non-enzymatic chemical synthesis of phospholipids to prepare proteoliposomes.
T32 GM007240/GM/NIGMS NIH HHS/United States GM007240/GM/NIGMS NIH HHS/United States GM008326/GM/NIGMS NIH HHS/United States 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 and Biochemistry, University of California, San Diego, 9500 Gilman Drive, Building: Urey Hall 4120, La Jolla, CA 92093 (USA) http://devarajgroup.ucsd.edu. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, Building: Urey Hall 4120, La Jolla, CA 92093 (USA) http://devarajgroup.ucsd.edu. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, Building: Pacific Hall 6160, La Jolla, CA 92093 (USA). Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, Building: Urey Hall 4120, La Jolla, CA 92093 (USA) http://devarajgroup.ucsd.edu. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, Building: Pacific Hall 6160, La Jolla, CA 92093 (USA). Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, Building: Urey Hall 4120, La Jolla, CA 92093 (USA) http://devarajgroup.ucsd.edu. ndevaraj@ucsd.edu. alt-title: Angewandte Chemie (International ed number: 43 accession-num: 26316292
Keywords: Animals; Proteolipids/*chemistry/metabolism; Membrane Proteins/*chemistry/metabolism; Cattle; Electron Transport Complex IV/chemistry/metabolism; Lipid Bilayers/*chemistry/metabolism; Micelles; Phospholipids/*chemistry/metabolism; Plasma Membrane Calcium-Transporting ATPases/chemistry/metabolism

Blocking of the PD-1/PD-L1 Interaction by a D-Peptide Antagonist for Cancer Immunotherapy - Chang, H. N.; Liu, B. Y.; Qi, Y. K.; Zhou, Y.; Chen, Y. P.; Pan, K. M.; Li, W. W.; Zhou, X. M.; Ma, W. W.; Fu, C. Y.; Qi, Y. M.; Liu, L.; et al. (Angew. Chem. Int. Ed., 2015)
Blockade of the protein-protein interaction between the transmembrane protein programmed cell death protein 1 (PD-1) and its ligand PD-L1 has emerged as a promising immunotherapy for treating cancers. Using the technology of mirror-image phage display, we developed the first hydrolysis-resistant D-peptide antagonists to target the PD-1/PD-L1 pathway. The optimized compound (D) PPA-1 could bind PD-L1 at an affinity of 0.51 muM in vitro. A blockade assay at the cellular level and tumor-bearing mice experiments indicated that (D) PPA-1 could also effectively disrupt the PD-1/PD-L1 interaction in vivo. Thus D-peptide antagonists may provide novel low-molecular-weight drug candidates for cancer immunotherapy.
Journal Article Germany
The following values have no corresponding Zotero field: auth-address: Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 (China). School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province (China). Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 (China). School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province (China). School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province (China). Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 (China). School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province (China). School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province (China). Tsinghua-Peking Center for Life Sciences, Laboratory of Dynamic Immunobiology, Institute for Immunobiology, School of Life Medicine, Tsinghua University, Beijing 100084 (China). School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province (China). School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province (China). Tsinghua-Peking Center for Life Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084 (China). lliu@mail.tsinghua.edu.cn. School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province (China). gaoyf@zzu.edu.cn. alt-title: Angewandte Chemie (International ed number: 40 accession-num: 26259671

Access to large cyclic peptides by a one-pot two-peptide segment ligation/cyclization process - Boll, E.; Ebran, J. P.; Drobecq, H.; El-Mahdi, O.; Raibaut, L.; Ollivier, N.; Melnyk, O. (Org. Lett., 2015)
The use of the N-acetoacetyl protecting group for N-terminal cysteine residue enabled creation of an efficient and mild one-pot native chemical ligation/SEA ligation sequence giving access to large cyclic peptides.
Boll, Emmanuelle Ebran, Jean-Philippe Drobecq, Herve El-Mahdi, Ouafaa Raibaut, Laurent Ollivier, Nathalie Melnyk, Oleg United States Organic letters Org Lett. 2015 Jan 2;17(1):130-3. doi: 10.1021/ol503359w. Epub 2014 Dec 15.
Cited By :15
Cited By :15
Export Date: 25 May 2018
Export Date: 25 May 2018

One-pot chemical synthesis of small ubiquitin-like modifier (SUMO) protein-peptide conjugates using bis(2-sulfanylethyl)amido peptide latent thioester surrogates - Boll, E.; Drobecq, H.; Ollivier, N.; Blanpain, A.; Raibaut, L.; Desmet, R.; Vicogne, J.; Melnyk, O. (Nat. Protoc., 2015)
Cited By :24
Cited By :24
Cited By :24
Export Date: 25 May 2018
Export Date: 25 May 2018
Keywords: #nosource

Chemical protein synthesis using a second-generation N-acylurea linker for the preparation of peptide-thioester precursors - Blanco-Canosa, Juan B.; Nardone, Brunello; Albericio, Fernando; Dawson, Philip E. (J. Am. Chem. Soc., 2015)
doi: 10.1021/jacs.5b03504 0002-7863 doi: 10.1021/jacs.5b03504
The following values have no corresponding Zotero field: number: 22 publisher: American Chemical Society

A PEGylated photocleavable auxiliary mediates the sequential enzymatic glycosylation and native chemical ligation of peptides - Bello, Claudia; Wang, Shuo; Meng, Lu; Moremen, Kelley W.; Becker, Christian F. W. (Angew. Chem. Int. Ed., 2015)
Research aimed at understanding the specific role of glycosylation patterns in protein function would greatly benefit from additional approaches allowing direct access to homogeneous glycoproteins. Herein the development and application of an efficient approach for the synthesis of complex homogenously glycosylated peptides based on a multifunctional photocleavable auxiliary is described. The presence of a PEG polymer within the auxiliary enables sequential enzymatic glycosylation and straightforward isolation in excellent yields. The auxiliary-modified peptides can be directly used in native chemical ligations with peptide thioesters easily obtained by direct hydrazinolysis of the respective glycosylated peptidyl resins and subsequent oxidation. The ligated glycopeptides can be smoothly deprotected by UV irradiation. We apply this approach to the preparation of variants of the epithelial tumor marker MUC1 carrying one or more Tn, T, or sialyl-T antigens.
The following values have no corresponding Zotero field: number: 26 publisher: WILEY-VCH Verlag
Keywords: bioorganic chemistry; chemoenzymatic glycosylation; PEGylation; photocleavable ligation auxiliary; protein modifications

Peptidyl N-alkylcysteine as a peptide thioester surrogate in the native chemical ligation - Asahina, Yuya; Nabeshima, Kei; Hojo, Hironobu (Tetrahedron Lett., 2015)
Peptides having the C-terminal N-alkylcysteine (NAC) with a free carboxy group, which can be easily prepared by the conventional 9-fluorenylmethoxycarbonyl (Fmoc) solid-phase peptide synthesis (SPPS), was directly used for the native chemical ligation (NCL) based on the in situ thioesterification method. The reaction efficiently proceeded under a mild acidic condition (pH ∼5) to give the ligated product. This method was successfully used for the synthesis of the human brain natriuretic peptide, (BNP)-32, showing the usefulness of the peptidyl NAC as a thioester surrogate for the NCL reaction.
The following values have no corresponding Zotero field: number: 11
Keywords: -Alkylcysteine (NAC); -to- acyl device; Native chemical ligation (NCL); Peptide thioester; Thioesterification

Expedient total synthesis of small to medium-sized membrane proteins via Fmoc chemistry - Zheng, Ji-Shen; Yu, Mu; Qi, Yun-Kun; Tang, Shan; Shen, Fei; Wang, Zhi-Peng; Xiao, Liang; Zhang, Longhua; Tian, Chang-Lin; Liu, Lei (J. Am. Chem. Soc., 2014)
The following values have no corresponding Zotero field: number: 9 publisher: American Chemical Society

Mirror image proteins - Zhao, L.; Lu, W. (Curr. Opin. Chem. Biol., 2014)
Proteins composed entirely of unnatural d-amino acids and the achiral amino acid glycine are mirror image forms of their native l-protein counterparts. Recent advances in chemical protein synthesis afford unique and facile synthetic access to domain-sized mirror image d-proteins, enabling protein research to be conducted through 'the looking glass' and in a way previously unattainable. d-Proteins can facilitate structure determination of their native l-forms that are difficult to crystallize (racemic X-ray crystallography); d-proteins can serve as the bait for library screening to ultimately yield pharmacologically superior d-peptide/d-protein therapeutics (mirror-image phage display); d-proteins can also be used as a powerful mechanistic tool for probing molecular events in biology. This review examines recent progress in the application of mirror image proteins to structural biology, drug discovery, and immunology.
The following values have no corresponding Zotero field: auth-address: First Affiliated Hospital, Xi'an Jiaotong University School of Medicine, China. Key Laboratory of Biomedical Information Engineering of the Ministry of Education, School of Life Science and Technology and Center for Translational Medicine, Frontier Institute of Science and Technology, Xi'an Jiaotong University, China; Institute of Human Virology and Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, USA. Electronic address: wlu@ihv.umaryland.edu. alt-title: Current opinion in chemical biology edition: 2014/10/06 accession-num: 25282524 work-type: Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review
Zhao, Le Lu, Wuyuan R01 GM106710/GM/NIGMS NIH HHS/ England Curr Opin Chem Biol. 2014 Oct;22:56-61. doi: 10.1016/j.cbpa.2014.09.019. Epub 2014 Oct 1.
Keywords: Animals; Humans; Models, Molecular; Protein Conformation; Stereoisomerism; Proteins/*chemistry; Crystallography, X-Ray/methods; Drug Discovery/methods

Formation and rearrangement of homoserine depsipeptides and depsiproteins in the alpha-ketoacid-hydroxylamine ligation with 5-oxaproline - Wucherpfennig, T. G.; Rohrbacher, F.; Pattabiraman, V. R.; Bode, J. W. (Angew. Chem. Int. Ed., 2014)
The primary products of the chemical ligation of alpha-ketoacids and 5-oxaproline peptides are esters, rather than the previously reported amides. The depsipeptide product rapidly rearranges to the amide in basic buffers. The formation of esters sheds light on possible mechanisms for the type II KAHA ligations and opens an avenue for the chemical synthesis of depsiproteins.
Journal Article Research Support, Non-U.S. Gov't Germany
The following values have no corresponding Zotero field: auth-address: Laboratorium fur Organische Chemie, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich (Switzerland) http://www.bode.ethz.ch. alt-title: Angewandte Chemie (International ed number: 45 accession-num: 25243600
Keywords: Amino Acid Sequence; Molecular Sequence Data; Hydroxylamines/*chemistry; Oligopeptides/*chemistry; Proline/*analogs & derivatives/chemistry

Characteristics of protein residue-residue contacts and their application in contact prediction - Wozniak, Pawel P.; Kotulska, Malgorzata (J. Mol. Model., 2014)
Contact sites between amino acids characterize important structural features of a protein. We investigated characteristics of contact sites in a representative set of proteins and their relations between protein class or topology. For this purpose, we used a non-redundant set of 5872 protein domains, identically categorized by CATH and SCOP databases. The proteins represented alpha, beta, and alpha+beta classes. Contact maps of protein structures were obtained for a selected set of physical distances in the main backbone and separations in protein sequences. For each set a dependency between contact degree and distance parameters was quantified. We indicated residues forming contact sites most frequently and unique amino acid pairs which created contact sites most often within each structural class. Contact characteristics of specific topologies were compared to the characteristics of their protein classes showing protein groups with a distinguished contact characteristic. We showed that our results could be used to improve the performance of recent top contact predictor — direct coupling analysis. Our work provides values of contact site propensities that can be involved in bioinformatic databases. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00894-014-2497-9) contains supplementary material, which is available to authorized users.
1610-2940 0948-5023 25374390[pmid] 2497[PII] 25374390[pmid] J Mol Model
The following values have no corresponding Zotero field: number: 11 pub-location: Berlin/Heidelberg publisher: Springer Berlin Heidelberg

Molecular grafting onto a stable framework yields novel cyclic peptides for the treatment of multiple sclerosis - Wang, C. K.; Gruber, C. W.; Cemazar, M.; Siatskas, C.; Tagore, P.; Payne, N.; Sun, G.; Wang, S.; Bernard, C. C.; Craik, D. J. (ACS Chem. Biol., 2014)
The following values have no corresponding Zotero field: auth-address: Institute for Molecular Bioscience, University of Queensland , Brisbane, QLD 4072, Australia. number: 1 edition: 2013/10/24 accession-num: 24147816
Keywords: Amino Acid Sequence; Animals; Humans; Models, Molecular; Molecular Sequence Data; Encephalomyelitis, Autoimmune, Experimental/prevention & control; Mice; Mice, Inbred C57BL; Multiple Sclerosis/immunology/*prevention & control; Myelin-Oligodendrocyte Glycoprotein/*chemistry/immunology/*therapeutic use; Peptides, Cyclic/*chemistry/immunology/*therapeutic use

Trifluoroethanethiol: an additive for efficient one-pot peptide ligation-desulfurization chemistry - Thompson, R. E.; Liu, X.; Alonso-Garcia, N.; Pereira, P. J.; Jolliffe, K. A.; Payne, R. J. (J. Am. Chem. Soc., 2014)
Native chemical ligation followed by desulfurization is a powerful strategy for the assembly of proteins. Here we describe the development of a high-yielding, one-pot ligation-desulfurization protocol that uses trifluoroethanethiol (TFET) as a novel thiol additive. The synthetic utility of this TFET-enabled methodology is demonstrated by the efficient multi-step one-pot syntheses of two tick-derived proteins, chimadanin and madanin-1, without the need for any intermediary purification.
Journal Article Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: School of Chemistry, The University of Sydney , Sydney, NSW 2006, Australia. alt-title: Journal of the American Chemical Society number: 23 accession-num: 24873761
Keywords: Chromatography, High Pressure Liquid; Mass Spectrometry; Chemistry Techniques, Synthetic; Insect Proteins/*chemical synthesis/*chemistry; Trifluoroethanol/*analogs & derivatives/chemistry

A novel post-ligation thioesterification device enables peptide ligation in the N to C direction: synthetic study of human glycodelin - Takenouchi, T.; Katayama, H.; Nakahara, Y.; Hojo, H. (J Pept Sci, 2014)
Human glycodelin consists of 162 amino acid residues and two N-linked glycans at Asn(28) and Asn(63) . In this study, we synthesized it by a fully convergent strategy using native chemical ligation (NCL) in N to C direction. The four peptide segments corresponding to 1-31, 32-65, 66-105 and 106-162 sequences were synthesized by 9-fluorenylmethoxycarbonyl based solid-phase peptide synthesis. At the C-terminus of the second segment, N-ethyl-S-acetamidomethyl-cysteine was attached as a post-ligation thioesterification device. The N-terminal two segments were condensed by the homocysteine-mediated NCL at Leu-Met site, and the product was methylated to convert homocysteine to methionine. After deprotection of acetamidomethyl group on the N-ethylcysteine residue, the peptide was thioesterified by N-alkylcysteine-assisted method. The product was then ligated with the C-terminal half, which was obtained by the NCL of third and fourth segments, to give the full-length glycodelin.
Takenouchi, Takaomi Katayama, Hidekazu Nakahara, Yuko Nakahara, Yoshiaki Hojo, Hironobu England J Pept Sci. 2014 Jan;20(1):55-61. doi: 10.1002/psc.2592. Epub 2013 Dec 12.
The following values have no corresponding Zotero field: auth-address: Department of Applied Biochemistry, Faculty of Engineering, Tokai University, 4-1-1 Kitakaname, Hiratsuka, Kanagawa, 259-1292, Japan. alt-title: Journal of peptide science : an official publication of the European Peptide Society number: 1 edition: 2013/12/21 accession-num: 24357164 work-type: Research Support, Non-U.S. Gov't
Keywords: Amino Acid Sequence; Humans; Cysteine/chemistry; Chromatography, High Pressure Liquid; Solid-Phase Synthesis Techniques; Amino Acids; Chromatography, Reverse-Phase; Esterification; Fluorenes; Glycodelin; Glycoproteins/*chemical synthesis/isolation & purification

Model study using designed selenopeptides on the importance of the catalytic triad for the antioxidative functions of glutathione peroxidase - Takei, T.; Urabe, Y.; Asahina, Y.; Hojo, H.; Nomura, T.; Dedachi, K.; Arai, K.; Iwaoka, M. (J Phys Chem B, 2014)
Although the catalytic triad of glutathione peroxidase (GPx) has been well recognized, there was little evidence for the relevance of the interactions among the triad amino acid residues, i.e., selenocysteine (U), glutamine (Q), and tryptophan (W), to the GPx antioxidative functions. Using a designed selenopeptide having an amino acid sequence of GQAUAWG, we demonstrate here that U, Q, and W present at the active site can interact with each other to exert the enzymatic activity. The amino acid sequence was chosen on the basis of the Monte Carlo molecular simulation for various selenopeptides in polarizable continuous water using the SAAP force field (SAAP-MC). Measurement of the GPx-like activity for the selenopeptide obtained by solid-phase peptide synthesis revealed that the antioxidant activity is cooperatively enhanced by the presence of Q and W proximate to U, although the activity was low compared to selenocystine (U2). The effect of Q on the activity was more important than that of W. In addition, the fluorescence spectrometry suggested a close contact between U and W. These experimental observations were supported by SAAP-MC simulation as well as by ab initio calculation. The latter further suggested that the interaction mode among the triad changes depending on the intermediate states.
Takei, Toshiki Urabe, Yoshiko Asahina, Yuya Hojo, Hironobu Nomura, Takeshi Dedachi, Kenichi Arai, Kenta Iwaoka, Michio J Phys Chem B. 2014 Jan 16;118(2):492-500. doi: 10.1021/jp4113975. Epub 2013 Dec 30.
The following values have no corresponding Zotero field: auth-address: Department of Chemistry, School of Science, Tokai University , Kitakaname, Hiratsuka-shi, Kanagawa 259-1292, Japan. alt-title: The journal of physical chemistry. B number: 2 edition: 2013/12/21 accession-num: 24354504 work-type: Research Support, Non-U.S. Gov't
Keywords: Amino Acid Sequence; Peptides/chemical synthesis/*chemistry; Biocatalysis; Antioxidants/*chemistry/metabolism; Catalytic Domain; Glutamine/chemistry; Glutathione Peroxidase/*chemistry/metabolism; Monte Carlo Method; Selenocysteine/*chemistry; Spectrometry, Fluorescence; Tryptophan/chemistry

Mechanistic insight into benzenethiol catalyzed amide bond formations from thioesters and primary amines - Stuhr-Hansen, N.; Bork, N.; Stromgaard, K. (Org. Biomol. Chem., 2014)
The influence of arylthiols on cysteine-free ligation, i.e. the reaction between an alkyl thioester and a primary amine forming an amide bond, was studied in a polar aprotic solvent. We reacted the ethylthioester of hippuric acid with cyclohexylamine in the absence or presence of various quantities of thiophenol (PhSH) in a slurry of disodium hydrogen phosphate in dry DMF. Quantitative conversions into the resulting amide were observed within a few hours in the presence of equimolar amounts of thiophenol. Ab initio calculations showed that the reaction mechanism in DMF is similar to the well-known aqueous reaction mechanism. The energy barrier of the catalyzed amidation reaction is approximately 40 kJ mol(-1) lower than the non-catalyzed amidation reaction. At least partially this can be explained by a hydrogen bond from the amine to the pi-electrons of the thiophenol, stabilizing the transition state in the aromatic thioester amidation reaction. Under similar conditions, cysteine-free ligation was achieved by coupling a fully side-chain protected 15 amino acid phosphopeptide thioester to the free N-terminal of a side-chain protected 9 amino acid peptide producing the corresponding 24 amino acid phosphopeptide.
Journal Article England
The following values have no corresponding Zotero field: auth-address: Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. alt-title: Organic & biomolecular chemistry number: 30 accession-num: 24967660
Keywords: Amino Acid Sequence; Kinetics; Molecular Conformation; Cysteine/chemistry; Catalysis; Molecular Sequence Data; Chromatography, High Pressure Liquid; Amides/*chemistry; Sulfhydryl Compounds/*chemistry; Thermodynamics; Amines/*chemistry; Esters/*chemistry; Gas Chromatography-Mass Spectrometry; Phenols/*chemistry; Phosphopeptides/chemistry; Time Factors

Inteins: nature's gift to protein chemists - Shah, Neel H.; Muir, Tom W. (Chem. Sci., 2014)
Inteins are auto-processing domains found in organisms from all domains of life. These proteins carry out a process known as protein splicing, which is a multi-step biochemical reaction comprised of both the cleavage and formation of peptide bonds. While the endogenous substrates of protein splicing are specific essential proteins found in intein-containing host organisms, inteins are also functional in exogenous contexts and can be used to chemically manipulate virtually any polypeptide backbone. Given this, protein chemists have exploited various facets of intein reactivity to modify proteins in myriad ways for both basic biological research as well as potential therapeutic applications. Here, we review the intein field, first focusing on the biological context and phylogenetic diversity of inteins, followed by a description of intein structure and biochemical function. Finally, we discuss prevalent intein-based technologies, focusing on their applications in chemical biology, followed by persistent caveats of intein chemistry and approaches to alleviate these shortcomings. The findings summarized herein describe two and a half decades of research, leading from a biochemical curiosity to the development of powerful protein engineering tools.
10.1039/C3SC52951G
The following values have no corresponding Zotero field: number: 2 publisher: The Royal Society of Chemistry

Reversible native chemical ligation: a facile access to dynamic covalent peptides - Ruff, Y.; Garavini, V.; Giuseppone, N. (J. Am. Chem. Soc., 2014)
The broad interest of using reversible covalent bonds in chemistry, in particular at its interfaces with biology and materials science, has been recently established through numerous examples in the literature. However, the challenging exchange of peptide fragments using a dynamic covalent peptide bond has not yet been achieved without enzymatic catalysis because of its high thermodynamic stability. Here we show that peptide fragments can be exchanged by a chemoselective and reversible native chemical ligation (NCL) which can take place at N-(methyl)-cysteine residues. This very mild reaction is efficient in aqueous solution, is buffered at physiological pH in the presence of dithiothreitol (DTT), and shows typical half-times of equilibration in the 10 h range.
Ruff, Yves Garavini, Valentina Giuseppone, Nicolas United States Journal of the American Chemical Society J Am Chem Soc. 2014 Apr 30;136(17):6333-9. doi: 10.1021/ja4129845. Epub 2014 Apr 18.
The following values have no corresponding Zotero field: auth-address: SAMS Research Group, University of Strasbourg, Institut Charles Sadron, CNRS, 23 rue du Loess, BP 84047, 67034 Strasbourg Cedex 2, France. number: 17 edition: 2014/04/11 accession-num: 24717128

Peptide-templated acyl transfer: a chemical method for the labeling of membrane proteins on live cells - Reinhardt, U.; Lotze, J.; Zernia, S.; Morl, K.; Beck-Sickinger, A. G.; Seitz, O. (Angew. Chem. Int. Ed., 2014)
The development of a method is described for the chemical labeling of proteins which occurs with high target specificity, proceeds within seconds to minutes, and offers a free choice of the reporter group. The method relies upon the use of peptide templates, which align a thioester and an N-terminal cysteinyl residue such that an acyl transfer reaction is facilitated at nanomolar concentrations. The protein of interest is N-terminally tagged with a 22 aa long Cys-E3 peptide (acceptor), which is capable of forming a coiled-coil with a reporter-armed K3 peptide (donor). This triggers the transfer of the reporter to the acceptor on the target protein. Because ligation of the two interacting peptides is avoided, the mass increase at the protein of interest is minimal. The method is exemplified by the rapid fluorescent labeling and fluorescence microscopic imaging of the human Y2 receptor on living cells.
Journal Article Research Support, Non-U.S. Gov't Germany
The following values have no corresponding Zotero field: auth-address: Institut fur Chemie, Humboldt-Universitat zu Berlin, Brook-Taylor-Strasse 2, 12489 Berlin (Germany). alt-title: Angewandte Chemie (International ed number: 38 accession-num: 25081195
Keywords: Humans; Peptides/*chemistry; *Staining and Labeling; HEK293 Cells; Cell Survival; Membrane Proteins/*analysis/*chemistry

Semisynthesis of biologically active glycoforms of the human cytokine interleukin 6 - Reif, A.; Siebenhaar, S.; Troster, A.; Schmalzlein, M.; Lechner, C.; Velisetty, P.; Gottwald, K.; Pohner, C.; Boos, I.; Schubert, V.; Rose-John, S.; Unverzagt, C. (Angew. Chem. Int. Ed., 2014)
Human interleukin 6 (IL-6) is a potent cytokine with immunomodulatory properties. As the influence of N-glycosylation on the in vivo activities of IL-6 could not be elucidated so far, a semisynthesis of homogeneous glycoforms of IL-6 was established by sequential native chemical ligation. The four cysteines of IL-6 are convenient for ligations and require only the short synthetic glycopeptide 43-48. The Cys-peptide 49-183 could be obtained recombinantly by cleavage of a SUMO tag. The fragment 1-42 was accessible by the simultaneous cleavage of two inteins, leading to the 1-42 thioester with the native N-terminus. Ligation and refolding studies showed that the inherently labile Asp-Pro bond 139-140 was detrimental for the sequential C- to N-terminal ligation. A reversed ligation sequence using glycopeptide hydrazides gave full-length IL-6 glycoproteins, which showed full bioactivity after efficient refolding and purification.
Journal Article Research Support, Non-U.S. Gov't Germany
The following values have no corresponding Zotero field: auth-address: Bioorganic Chemistry, Gebaeude NWI, University of Bayreuth, 95440 Bayreuth (Germany). alt-title: Angewandte Chemie (International ed number: 45 accession-num: 25243720
Keywords: Humans; Chromatography, High Pressure Liquid; Mass Spectrometry; Interleukin-6/*chemical synthesis/chemistry; Protein Isoforms/*chemical synthesis/chemistry

In situ generation of redox active peptides driven by selenoester mediated native chemical ligation - Rasale, Dnyaneshwar B.; Maity, Indrajit; Das, Apurba K. (Chem. Commun., 2014)
Redox active peptides are generated through selenoester mediated native chemical ligation (NCL). Distinct nanostructures, such as nanotubes to nanofibrillar architectures, were observed for self-assembling soft materials.
1359-7345 10.1039/C4CC03835E
The following values have no corresponding Zotero field: number: 77 publisher: The Royal Society of Chemistry

Synthesis of nucleoside phosphate and phosphonate prodrugs - Pradere, Ugo; Garnier-Amblard, Ethel C.; Coats, Steven J.; Amblard, Franck; Schinazi, Raymond F. (Chem. Rev., 2014)
0009-2665 1520-6890 25144792[pmid] Chem Rev
The following values have no corresponding Zotero field: number: 18 publisher: American Chemical Society

Pharmacogenetics and the Immunogenicity of Protein Therapeutics - Pandey, G. S.; Sauna, Z. E. (J Interferon Cytokine Res, 2014)
The recognition that genetic factors influence the heterogeneity of individual responses to medications with respect to both toxicity and efficacy is not new. However, only following dramatic advances in functional genomics during the last decade did the development of so-called personalized medicine become a realistic possibility. Although drug development approaches that integrate pharmacogenetic information about both the protein drug and its protein target appear logical, given the complexity of biological systems, the selection of appropriate biomarkers and the study design remain daunting tasks. Here we present potential applications of pharmacogenetics in the development of recombinant coagulation factors. In addition, we highlight the potential utility of a personalized approach to predicting and eventually circumventing immunogenicity using the recombinant Factor VIII in the treatment of hemophilia A as a model system. The immunogenicity of protein therapeutics is of increasing concern during the development and licensure of biologics and clearly calls for a pharmacogenetic approach. This is because, with immunogenicity, the predicament is not that all patients develop inhibitory antibodies but that some individuals, ethnicities, or other subpopulations have a stronger immunogenic reaction than others do.
Journal article the official journal of the International Society for Interferon and Cytokine Research
The following values have no corresponding Zotero field: auth-address: Laboratory of Hemostasis, Division of Hematology, Center for Biologics Evaluation and Research , Food and Drug Administration, Bethesda, Maryland. number: 12 accession-num: 25493960

Traceless chemical ligation from S-, O-, and N-acyl isopeptides - Panda, Siva S.; Hall, C. Dennis; Oliferenko, Alexander A.; Katritzky, Alan R. (Acc. Chem. Res., 2014)
doi: 10.1021/ar400242q 0001-4842 doi: 10.1021/ar400242q
The following values have no corresponding Zotero field: number: 4 publisher: American Chemical Society

One-pot hydrazide-based native chemical ligation for efficient chemical synthesis and structure determination of toxin Mambalgin-1 - Pan, Man; He, Yao; Wen, Ming; Wu, Fangming; Sun, Demeng; Li, Sijian; Zhang, Longhua; Li, Yiming; Tian, Changlin (Chem. Commun., 2014)
An efficient one-pot chemical synthesis of snake venom toxin Mambalgin-1 was achieved using an azide-switch strategy combined with hydrazide-based native chemical ligation. Synthetic Mambalgin-1 exhibited a well-defined structure after sequential folding in vitro. NMR spectroscopy revealed a three-finger toxin family structure, and the synthetic toxin inhibited human acid-sensing ion channel 1a.
1359-7345 10.1039/C4CC00779D
The following values have no corresponding Zotero field: number: 44 publisher: The Royal Society of Chemistry

Tidbits for the synthesis of bis(2-sulfanylethyl)amido (SEA) polystyrene resin, SEA peptides and peptide thioesters - Ollivier, Nathalie; Raibaut, Laurent; Blanpain, Annick; Desmet, Rémi; Dheur, Julien; Mhidia, Reda; Boll, Emmanuelle; Drobecq, Hervé; Pira, Silvain L.; Melnyk, Oleg (J. Pept. Sci., 2014)
Cited By :13
Cited By :13
Export Date: 25 May 2018
Export Date: 25 May 2018
The following values have no corresponding Zotero field: number: 2
Keywords: bis(2-sulfanylethyl)amido (SEA); Fmoc-SPPS; thioester; thiol exchange

Selenopeptide transamidation and metathesis - Ollivier, Nathalie; Blanpain, Annick; Boll, Emmanuelle; Raibaut, Laurent; Drobecq, Hervé; Melnyk, Oleg (Org. Lett., 2014)
Cited By :11
Cited By :11
doi: 10.1021/ol501866j 1523-7060 doi: 10.1021/ol501866j
Export Date: 25 May 2018
Export Date: 25 May 2018

Examination of native chemical ligation using peptidyl prolyl thioesters - Nakamura, Takahiro; Shigenaga, Akira; Sato, Kohei; Tsuda, Yusuke; Sakamoto, Ken; Otaka, Akira (Chem. Commun., 2014)
Peptidyl prolyl thioesters, which have been regarded as too unreactive for practical use in native chemical ligations (NCLs), were proven to be versatile reagents in peptide coupling. Tuning the reactivity of prolyl thioesters enabled a one-pot/sequential NCL reaction based on kinetically controlled ligation.
10.1039/C3CC47228K
The following values have no corresponding Zotero field: number: 1 publisher: The Royal Society of Chemistry

Postsynthetic modification of unprotected peptides via S-tritylation reaction - Mochizuki, Masayoshi; Hibino, Hajime; Nishiuchi, Yuji (Org. Lett., 2014)
The following values have no corresponding Zotero field: number: 21 publisher: American Chemical Society

The species- and site-specific acid–base properties of biological thiols and their homodisulfides - Mirzahosseini, Arash; Noszál, Béla (J. Pharm. Biomed. Anal., 2014)
Cysteamine, cysteine, homocysteine, their homodisulfides and 9 related compounds were studied by 1H NMR-pH titrations and case-tailored evaluation methods. The resulting acid–base properties are quantified in terms of 33 macroscopic and 62 microscopic protonation constants and the concomitant 16 interactivity parameters, providing thus the first complete microspeciation of this vitally important family of biomolecules. The species- and site-specific basicities are interpreted by means of inductive and hydrogen-bonding effects through various intra- and intermolecular comparisons. The pH-dependent distribution of the microspecies is depicted. The thiolate basicities determined this way provide exclusive means for the prediction of thiolate oxidizabilities, a key parameter to understand and influence oxidative stress at the molecular level.
Keywords: Disulfide; Microspeciation; Oxidizability; pKa; Thiol

Natural and synthetic selenoproteins - Metanis, N.; Hilvert, D. (Curr. Opin. Chem. Biol., 2014)
Once considered highly toxic, the element selenium is now recognized as a micronutrient essential for human health. It is inserted co-translationally into many proteins as the non-canonical amino acid selenocysteine, providing the resulting selenoprotein molecules with a range of valuable redox properties; selenocysteine is also increasingly exploited as a structural and mechanistic probe in synthetic peptides and proteins. Here we review topical investigations into the preparation and characterization of natural and artificial selenoproteins. Such molecules are uniquely suited as tools for protein chemistry and as a test bed for studying novel catalytic activities.
Journal Article Research Support, Non-U.S. Gov't Review England
The following values have no corresponding Zotero field: auth-address: Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel. Electronic address: metanis@mail.huji.ac.il. Laboratory of Organic Chemistry, ETH Zurich, 8093 Zurich, Switzerland. Electronic address: hilvert@org.chem.ethz.ch. alt-title: Current opinion in chemical biology accession-num: 25261915
Keywords: Animals; Humans; Oxidation-Reduction; Protein Folding; Protein Biosynthesis; Recombinant Proteins/chemical synthesis/chemistry/genetics/metabolism; Selenocysteine/chemical synthesis/*chemistry/genetics/metabolism; Selenoproteins/chemical synthesis/*chemistry/genetics/metabolism

Phenylthiocarbamate or N-carbothiophenyl group chemistry in peptide synthesis and bioconjugation - Melnyk, O.; Ollivier, N.; Besret, S.; Melnyk, P. (Bioconjugate Chem., 2014)
The design of novel chemoselective and site-specific ligation methods provides new tools for obtaining complex scaffolds, peptidomimetics, and peptide conjugates. The chemistry of the N-phenylthiocarbonyl group has led to several developments in peptide ligation chemistry and peptide bioconjugation during the last 10 years. The aim of this review is to provide an overview of this emerging field.
Cited By :4
Export Date: 25 May 2018
Melnyk, Oleg Ollivier, Nathalie Besret, Soizic Melnyk, Patricia United States Bioconjugate chemistry Bioconjug Chem. 2014 Apr 16;25(4):629-39. doi: 10.1021/bc500052r. Epub 2014 Mar 28.
The following values have no corresponding Zotero field: auth-address: UMR CNRS 8161 , F-59021 Lille, France. number: 4 edition: 2014/03/20 accession-num: 24641212

From protein total synthesis to peptide transamidation and metathesis: playing with the reversibility of N,S-acyl or N,Se-acyl migration reactions - Melnyk, Oleg; Agouridas, Vangelis (Curr. Opin. Chem. Biol., 2014)
Amide forming reactions are central to the field of peptide and protein synthesis and are considered to be poorly reversible reactions owing to the high stability of peptide bonds. One amide-forming reaction is native chemical ligation (NCL) which is driven by a sulfur to nitrogen acyl migration process from a transient thioester intermediate. However, recent studies have revealed the reversibility of the S,N-acyl shift reaction or of the related Se,N-acyl shift process using mild aqueous conditions. Such chemical processes have great potential for the chemoselective formation of peptide bonds to cysteine or selenocysteine, and open novel avenues in the field of peptide transamidation and metathesis reactions.

Perhydro-1,2,5-dithiazepine - Melnyk, O.; Agouridas, V. (e-EROS, 2014)
Keywords: #nosource

Peptide ligation chemistry at selenol amino acids - Malins, L. R.; Mitchell, N. J.; Payne, R. J. (J Pept Sci, 2014)
The convergent assembly of peptide fragments by native chemical ligation has revolutionized the way in which proteins can be accessed by chemical synthesis. A variation of native chemical ligation involves the reaction of peptides bearing an N-terminal selenocysteine residue with peptide thioesters, which proceeds through the same mechanism as the parent reaction. This transformation was first investigated in 2001 for the installation of selenocysteine into peptides and proteins via ligation chemistry. The recent discovery that selenocysteine residues within peptides can be chemoselectively deselenized without the concomitant desulfurization of cysteine residues has led to renewed interest in ligation chemistry at selenocysteine. This review outlines the use of selenocysteine in ligation chemistry as well as recent investigations of chemoselective ligation-deselenization chemistry at other selenol-derived amino acids that have the potential to greatly expand the number of targets that can be accessed by chemical synthesis.
Journal Article Review England an official publication of the European Peptide Society
The following values have no corresponding Zotero field: auth-address: School of Chemistry, The University of Sydney, Sydney, NSW, 2006, Australia. School of Chemistry, The University of Sydney, Sydney, NSW, 2006, Australia. School of Chemistry, The University of Sydney, Sydney, NSW, 2006, Australia. number: 2 accession-num: 24285588
Keywords: Molecular Structure; Amino Acids/chemistry/*metabolism; Peptides/chemistry/metabolism; Selenium Compounds/*chemistry; Selenocysteine/chemistry/metabolism

Evolutionary importance of the intramolecular pathways of hydrolysis of phosphate ester mixed anhydrides with amino acids and peptides - Liu, Z.; Beaufils, D.; Rossi, J. C.; Pascal, R. (Sci. Rep., 2014)
Aminoacyl adenylates (aa-AMPs) constitute essential intermediates of protein biosynthesis. Their polymerization in aqueous solution has often been claimed as a potential route to abiotic peptides in spite of a highly efficient CO2-promoted pathway of hydrolysis. Here we investigate the efficiency and relevance of this frequently overlooked pathway from model amino acid phosphate mixed anhydrides including aa-AMPs. Its predominance was demonstrated at CO2 concentrations matching that of physiological fluids or that of the present-day ocean, making a direct polymerization pathway unlikely. By contrast, the occurrence of the CO2-promoted pathway was observed to increase the efficiency of peptide bond formation owing to the high reactivity of the N-carboxyanhydride (NCA) intermediate. Even considering CO2 concentrations in early Earth liquid environments equivalent to present levels, mixed anhydrides would have polymerized predominantly through NCAs. The issue of a potential involvement of NCAs as biochemical metabolites could even be raised. The formation of peptide-phosphate mixed anhydrides from 5(4H)-oxazolones (transiently formed through prebiotically relevant peptide activation pathways) was also observed as well as the occurrence of the reverse cyclization process in the reactions of these mixed anhydrides. These processes constitute the core of a reaction network that could potentially have evolved towards the emergence of translation.
Journal Article Research Support, Non-U.S. Gov't England
The following values have no corresponding Zotero field: auth-address: Institut des Biomolecules Max Mousseron, UMR5247 CNRS - University of Montpellier. Institut des Biomolecules Max Mousseron, UMR5247 CNRS - University of Montpellier. Institut des Biomolecules Max Mousseron, UMR5247 CNRS - University of Montpellier. Institut des Biomolecules Max Mousseron, UMR5247 CNRS - University of Montpellier. alt-title: Scientific reports accession-num: 25501391
Keywords: Peptides/*chemistry; Esters; Hydrolysis; *Evolution, Molecular; Amino Acids/*chemistry; Anhydrides/*chemistry; Metabolic Networks and Pathways; Phosphates/chemistry

Structural model for covalent adhesion of the Streptococcus pyogenes pilus through a thioester bond - Linke-Winnebeck, C.; Paterson, N. G.; Young, P. G.; Middleditch, M. J.; Greenwood, D. R.; Witte, G.; Baker, E. N. (J. Biol. Chem., 2014)
The human pathogen Streptococcus pyogenes produces pili that are essential for adhesion to host surface receptors. Cpa, the adhesin at the pilus tip, was recently shown to have a thioester-containing domain. The thioester bond is believed to be important in adhesion, implying a mechanism of covalent attachment analogous to that used by human complement factors. Here, we have characterized a second active thioester-containing domain on Cpa, the N-terminal domain of Cpa (CpaN). Expression of CpaN in Escherichia coli gave covalently linked dimers. These were shown by x-ray crystallography and mass spectrometry to comprise two CpaN molecules cross-linked by the polyamine spermidine following reaction with the thioester bonds. This cross-linked CpaN dimer provides a model for the covalent attachment of Cpa to target receptors and thus the streptococcal pilus to host cells. Similar thioester domains were identified in cell wall proteins of other Gram-positive pathogens, suggesting that thioester domains are more widely used and provide a mechanism of adhesion by covalent bonding to target molecules on host cells that mimics that used by the human complement system to eliminate pathogens.
Journal Article Research Support, Non-U.S. Gov't United States
The following values have no corresponding Zotero field: auth-address: From the School of Biological Sciences and Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Private Bag 921019, Auckland 1142, New Zealand and. alt-title: The Journal of biological chemistry number: 1 accession-num: 24220033
Keywords: Humans; Molecular Sequence Data; *Models, Molecular; Protein Structure, Quaternary; *Protein Multimerization; Adhesins, Bacterial/*chemistry/genetics/metabolism; Base Sequence; Complement System Proteins/chemistry/genetics/metabolism; Crystallography, X-Ray; Escherichia coli; Fimbriae, Bacterial/*chemistry/genetics/metabolism; Protein Structure, Tertiary; Streptococcus pyogenes/*chemistry/genetics/pathogenicity

Irreversible site-specific hydrazinolysis of proteins by use of sortase - Li, Yi-Ming; Li, Yi-Tong; Pan, Man; Kong, Xiu-Qi; Huang, Yi-Chao; Hong, Zhang-Yong; Liu, Lei (Angew. Chem. Int. Ed., 2014)
Sortase-mediated hydrazinolysis of proteins with hydrazine or its derivatives was developed for the production of recombinant protein hydrazides. This process provides an alternative approach for protein semisynthesis through the use of recombinant protein hydrazides as thioester surrogates. It also provides an alternative method for C-terminal modification of proteins with functional units as well as for the preparation of C-to-C fusion proteins.
The following values have no corresponding Zotero field: number: 8 publisher: WILEY-VCH Verlag
Keywords: proteins; hydrazones; hydrolysis; ligation; protein modification

One-pot native chemical ligation of peptide hydrazides enables total synthesis of modified histones - Li, Jiabin; Li, Yuanyuan; He, Qiaoqiao; Li, Yiming; Li, Haitao; Liu, Lei (Org. Biomol. Chem., 2014)
One of the rising demands in the field of protein chemical synthesis is the development of facile strategies that yield the protein in workable quantities and homogeneity, with fewer handling steps. Although the native chemical ligation of peptide hydrazides has recently been shown to be useful for the chemical synthesis of proteins carrying acid-sensitive modification groups, previous hydrazide-based protein synthesis studies have used sequential ligation strategies. Here, we report a practical method for a "one-pot" native chemical ligation of peptide hydrazides that would circumvent the need for the isolation of the intermediate products. This method employed a fast and selective arylboronate oxidation reaction mediated by H2O2, which draws attention to the potential applications of the thus far under-exploited boron-based functionalities in protein chemical synthesis. To demonstrate the practicality and efficiency of the new one-pot method, we report its application to a scalable total synthesis of modified histones (with five analogues of H3 and H4 as examples) on a multi-milligram scale, with good homogeneity.
10.1039/C4OB00715H
The following values have no corresponding Zotero field: number: 29 publisher: The Royal Society of Chemistry

A Journey to the Total Synthesis of Daptomycin - Lam, Hiu Yung; Gaarden, Rannveig Ingebrigtsen; Li, Xuechen (Chem. Rec., 2014)
Daptomycin, the first antibiotic of its class, provides a new structural motif for the development of new antibiotics. Recently, we have completed the total synthesis of daptomycin. The development of the successful synthetic strategy is described here, including the application of serine/threonine ligation mediated peptide cyclization to the daptomycin macrocyclization.
1528-0691
The following values have no corresponding Zotero field: number: 6
Keywords: peptides; antibiotics; cyclization; daptomycin; total synthesis

Recent progress in the chemical synthesis of proteins - Hojo, H. (Curr. Opin. Struct. Biol., 2014)
A methodology for chemical protein synthesis by ligation chemistry has become increasingly practical and applied to the synthesis of various proteins and glycoproteins for their structural and functional analyses. This is largely due to the advances in the synthesis of peptide thioester as well as to the progress in the extension of the ligation chemistry to a non-cysteine site, which are briefly summarized in this review.
Hojo, Hironobu Review Current opinion in structural biology Curr Opin Struct Biol. 2014 Mar 26;26C:16-23. doi: 10.1016/j.sbi.2014.03.002.
The following values have no corresponding Zotero field: auth-address: Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Osaka 565-0871, Japan. Electronic address: hojo@protein.osaka-u.ac.jp. edition: 2014/04/01 accession-num: 24681507