Chemical proteomic profiling of protein N-homocysteinylation with a thioester probe.

ABSTRACT: Hyperhomocysteinemia (HHcy) refers to a medical condition of abnormally high level of homocysteine (Hcy) in blood (>15 μmol L-1) and has been clinically implicated with cardiovascular diseases and neurodegenerative disorders. Excessive Hcy can be converted to a reactive thioester intermediate, Hcy thiolactone (HTL), which selectively reacts with protein lysine residues ("N-homocysteinylation") and this non-enzymatic modification largely contributes to manifestations of HHcy. However, the proteome-wide detection of protein N-homocysteinylation remains a challenge to date. In this work, we report a chemoselective reaction to label and enrich N-homocysteinylation from complex proteome samples as inspired by native chemical ligation for protein synthesis. Alkynyl thioester probes are synthesiz

SUBMITTER: Chen N 

PROVIDER: S-EPMC5914431 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature