Cyclization of N-terminal S-carbamoylmethylcysteine causing loss of 17 Da from peptides and extra peaks in peptide maps

被引：50

作者：

Geoghegan, KF ^{[1
]}

Hoth, LR ^{[1
]}

Tan, DH ^{[1
]}

Borzillerl, KA ^{[1
]}

Withka, JM ^{[1
]}

Boyd, JG ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, Groton, CT 06340 USA

来源：

JOURNAL OF PROTEOME RESEARCH | 2002年 / 1卷 / 02期

关键词：

iodoacetamide; peptide mapping; cyclization; mass spectrometry; S-carbamoylmethylcysteine;

D O I：

10.1021/pr025503d

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Enzymatic digests of proteins S-alkylated with iodoacetamide may contain peptides with N-terminal S-carbamoylmethylcysteine. These can be partly converted to a form with 17 Da lower mass and increased HPLC retention. Proof by synthesis supported by MS/MS and NMR spectroscopy was used to show that N-terminal S-carbamoylmethyl-L-cysteine can cyclize, losing NH3 to form an N-terminal residue of (R)-5-oxoperhydro-1,4-thiazine-3-carboxylic acid. The abbreviation Otc is proposed for the (R)-5-oxoperhydro-1,4-thiazine-3-carbonyl residue. The rate of cyclization is significant in 0.1 M NH4-HCO3 at 37 degreesC, with the half-life of the acyclic form being 10-12 h for several peptides tested. This is similar to the rate at which N-terminal pyroglutamate forms from N-terminal glutamine.

引用

页码：181 / 187

页数：7