Chemical proteomic analysis of palmostatin beta-lactone analogs that affect N-Ras palmitoylation.

ABSTRACT: S-Palmitoylation is a reversible post-translational lipid modification that regulates protein trafficking and signaling. The enzymatic depalmitoylation of proteins is inhibited by the beta-lactones Palmostatin M and B, which have been found to target several serine hydrolases. In efforts to better understand the mechanism of action of Palmostatin M, we describe herein the synthesis, chemical proteomic analysis, and functional characterization of analogs of this compound. We identify Palmostatin M analogs that maintain inhibitory activity in N-Ras depalmitoylation assays while displaying complementary reactivity across the serine hydrolase class as measured by activity-based protein profiling. Active Palmostatin M analogs inhibit the recently characterized ABHD17 subfamily of depalmitoylati

SUBMITTER: Suciu RM 

PROVIDER: S-EPMC8896339 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature