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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Royal Society of Chemistry
2018
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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. |
format | Online Article Text |
id | pubmed-5892131 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
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
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title_full | Traceless β-mercaptan-assisted activation of valinyl benzimidazolinones in peptide ligations
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title_fullStr | Traceless β-mercaptan-assisted activation of valinyl benzimidazolinones in peptide ligations
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title_full_unstemmed | Traceless β-mercaptan-assisted activation of valinyl benzimidazolinones in peptide ligations
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title_short | Traceless β-mercaptan-assisted activation of valinyl benzimidazolinones in peptide ligations
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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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