Proteomic Ligandability Maps of Phosphorus(V) Stereoprobes Identify Covalent TLCD1 Inhibitors.

ABSTRACT: Activity-based protein profiling (ABPP) of stereoisomerically defined sets of electrophilic compounds ('stereoprobes') offers a versatile way to discover covalent ligands for proteins in native biological systems. Here we report the synthesis and chemical proteomic characterization of stereoprobes bearing a P(V)-oxathiaphospholane (OTP) reactive group. ABPP experiments identified numerous proteins in human cancer cells that showed stereoselective reactivity with OTP stereoprobes, and we confirmed several of these liganding events with recombinant proteins. OTP stereoprobes engaging the poorly characterized transmembrane protein TLCD1 impaired the incorporation of monounsaturated fatty acids into phosphatidylethanolamine lipids in cells, a lipidomic phenotype that mirrored genetic disruptio

SUBMITTER: Sharma HA 

PROVIDER: S-EPMC11838393 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature