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Selective Bi‐directional Amide Bond Cleavage of N ‐Methylcysteinyl Peptide
Author(s) -
Qiu Yibo,
Hemu Xinya,
Liu Ding Xiang,
Tam James P.
Publication year - 2014
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201402261
Subject(s) - thioester , chemistry , peptide bond , oxazolone , stereochemistry , cleavage (geology) , peptide , bond cleavage , amide , cysteine , thioamide , native chemical ligation , isomerization , cyclic peptide , organic chemistry , biochemistry , catalysis , enzyme , geotechnical engineering , fracture (geology) , engineering
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 N α ‐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 H 0 = –5, the MeCys‐Yaa bond underwent a C α ‐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.