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Traceless β-mercaptan-assisted activation of valinyl benzimidazolinones in peptide ligations

Peptidyl thioesters or their surrogates with C-terminal β-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 Va...

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Detalles Bibliográficos
Autores principales: Wang, Yinglu, Han, Lin, Yuan, Ning, Wang, Hanxuan, Li, Hongxing, Liu, Jinrong, Chen, Huan, Zhang, Qiang, Dong, Suwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892131/
https://www.ncbi.nlm.nih.gov/pubmed/29675240
http://dx.doi.org/10.1039/c7sc04148a
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author Wang, Yinglu
Han, Lin
Yuan, Ning
Wang, Hanxuan
Li, Hongxing
Liu, Jinrong
Chen, Huan
Zhang, Qiang
Dong, Suwei
author_facet Wang, Yinglu
Han, Lin
Yuan, Ning
Wang, Hanxuan
Li, Hongxing
Liu, Jinrong
Chen, Huan
Zhang, Qiang
Dong, Suwei
author_sort Wang, Yinglu
collection PubMed
description Peptidyl thioesters or their surrogates with C-terminal β-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 β-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 β-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 β-LPH and hPTH analogues, based on a kinetically controlled one-pot three-segment ligation and desulfurization strategy.
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spelling pubmed-58921312018-04-19 Traceless β-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 Chemistry Peptidyl thioesters or their surrogates with C-terminal β-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 β-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 β-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 β-LPH and hPTH analogues, based on a kinetically controlled one-pot three-segment ligation and desulfurization strategy. Royal Society of Chemistry 2018-01-05 /pmc/articles/PMC5892131/ /pubmed/29675240 http://dx.doi.org/10.1039/c7sc04148a Text en This journal is © The Royal Society of Chemistry 2018 http://creativecommons.org/licenses/by/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence (CC BY 3.0)
spellingShingle Chemistry
Wang, Yinglu
Han, Lin
Yuan, Ning
Wang, Hanxuan
Li, Hongxing
Liu, Jinrong
Chen, Huan
Zhang, Qiang
Dong, Suwei
Traceless β-mercaptan-assisted activation of valinyl benzimidazolinones in peptide ligations
title Traceless β-mercaptan-assisted activation of valinyl benzimidazolinones in peptide ligations
title_full Traceless β-mercaptan-assisted activation of valinyl benzimidazolinones in peptide ligations
title_fullStr Traceless β-mercaptan-assisted activation of valinyl benzimidazolinones in peptide ligations
title_full_unstemmed Traceless β-mercaptan-assisted activation of valinyl benzimidazolinones in peptide ligations
title_short Traceless β-mercaptan-assisted activation of valinyl benzimidazolinones in peptide ligations
title_sort traceless β-mercaptan-assisted activation of valinyl benzimidazolinones in peptide ligations
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892131/
https://www.ncbi.nlm.nih.gov/pubmed/29675240
http://dx.doi.org/10.1039/c7sc04148a
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