A Selective Chemical Probe for Coenzyme A-Requiring Enzymes

摘要

Structural and functional annotation of the human proteome is one of the critical challenges in biomedical research. Recent chemical approaches have been brought to bear on systematically interrogating enzymes involved in protein phosphorylation, proteolysis, lipid modification, glycosylation, deimi-nation, methyl transfer, and acetylation. An elegant strategy for analyzing substrates of acetyltransferases by using chlor-oacetyl coenzyme A (CoA) has been reported. However, to our knowledge, no chemical probes have yet been established to specifically tag CoA-dependent proteins by covalent cross-linking. These probes could be especially useful in the identification and analysis of histone and protein acetyltransferases, which contain many families with limited homology. Herein, we describe the synthesis and functional analysis of a new CoA chemical probe that shows selectivity in tagging acetyltransferases.