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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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. |
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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 |
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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. |
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School of Biological Sciences |
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School of Biological Sciences Qiu, Yibo Hemu, Xinya Liu, Ding Xiang Tam, James P. |
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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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1681038849879310336 |