Selective bi-directional amide bond cleavage of N-methylcysteinyl peptide

A selective bi-directional peptide bond cleavage mediated by N-methylcysteine (MeCys) in Xaa-MeCys-Yaa peptides (Xaa and Yaa, non-cysteine residues) leading to thioesters and thiolactones is described. Rate and product analyses showed that an Nα-amide bond cleavage occurred at the Xaa-MeCys bond by...

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Main Authors: Qiu, Yibo, Hemu, Xinya, Liu, Ding Xiang, Tam, James P.
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2014
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Online Access:https://hdl.handle.net/10356/103981
http://hdl.handle.net/10220/20068
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1039812020-03-07T12:24:54Z Selective bi-directional amide bond cleavage of N-methylcysteinyl peptide Qiu, Yibo Hemu, Xinya Liu, Ding Xiang Tam, James P. School of Biological Sciences DRNTU::Science::Chemistry::Organic chemistry A selective bi-directional peptide bond cleavage mediated by N-methylcysteine (MeCys) in Xaa-MeCys-Yaa peptides (Xaa and Yaa, non-cysteine residues) leading to thioesters and thiolactones is described. Rate and product analyses showed that an Nα-amide bond cleavage occurred at the Xaa-MeCys bond by an N–S acyl shift to generate an Xaa-S-(MeCys-Yaa) thioester at pH 1–5, whereas under strongly acidic conditions of H0 = –5, the MeCys-Yaa bond underwent a Cα-amide bond cleavage via an oxazolone intermediate, which was trapped by thiocresol (TC) as an Xaa-MeCys-TC thioester. This thioester was then transformed into an Xaa-MeCys-β-thiolactone at pH 4–5. Replacing MeCys by a Cys residue did not result in significant bi-directional peptide bond cleavage, which suggests that N-methylation in a MeCys residue is important for the N–S acyl shift reaction and formation of oxazolone. The isomerization of amides and thioesters was successfully used to prepare cyclic peptides. 2014-07-04T01:41:01Z 2019-12-06T21:23:55Z 2014-07-04T01:41:01Z 2019-12-06T21:23:55Z 2014 2014 Journal Article Qiu, Y., Hemu, X., Liu, D. X., & Tam, J. P. (2014). Selective Bi-directional Amide Bond Cleavage of N-Methylcysteinyl Peptide. European Journal of Organic Chemistry, 2014(20), 4370-4380. 1434-193X https://hdl.handle.net/10356/103981 http://hdl.handle.net/10220/20068 10.1002/ejoc.201402261 en European journal of organic chemistry © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
institution Nanyang Technological University
building NTU Library
country Singapore
collection DR-NTU
language English
topic DRNTU::Science::Chemistry::Organic chemistry
spellingShingle DRNTU::Science::Chemistry::Organic chemistry
Qiu, Yibo
Hemu, Xinya
Liu, Ding Xiang
Tam, James P.
Selective bi-directional amide bond cleavage of N-methylcysteinyl peptide
description A selective bi-directional peptide bond cleavage mediated by N-methylcysteine (MeCys) in Xaa-MeCys-Yaa peptides (Xaa and Yaa, non-cysteine residues) leading to thioesters and thiolactones is described. Rate and product analyses showed that an Nα-amide bond cleavage occurred at the Xaa-MeCys bond by an N–S acyl shift to generate an Xaa-S-(MeCys-Yaa) thioester at pH 1–5, whereas under strongly acidic conditions of H0 = –5, the MeCys-Yaa bond underwent a Cα-amide bond cleavage via an oxazolone intermediate, which was trapped by thiocresol (TC) as an Xaa-MeCys-TC thioester. This thioester was then transformed into an Xaa-MeCys-β-thiolactone at pH 4–5. Replacing MeCys by a Cys residue did not result in significant bi-directional peptide bond cleavage, which suggests that N-methylation in a MeCys residue is important for the N–S acyl shift reaction and formation of oxazolone. The isomerization of amides and thioesters was successfully used to prepare cyclic peptides.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Qiu, Yibo
Hemu, Xinya
Liu, Ding Xiang
Tam, James P.
format Article
author Qiu, Yibo
Hemu, Xinya
Liu, Ding Xiang
Tam, James P.
author_sort Qiu, Yibo
title Selective bi-directional amide bond cleavage of N-methylcysteinyl peptide
title_short Selective bi-directional amide bond cleavage of N-methylcysteinyl peptide
title_full Selective bi-directional amide bond cleavage of N-methylcysteinyl peptide
title_fullStr Selective bi-directional amide bond cleavage of N-methylcysteinyl peptide
title_full_unstemmed Selective bi-directional amide bond cleavage of N-methylcysteinyl peptide
title_sort selective bi-directional amide bond cleavage of n-methylcysteinyl peptide
publishDate 2014
url https://hdl.handle.net/10356/103981
http://hdl.handle.net/10220/20068
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