Chemical probes for profiling fatty acid-associated proteins in living cells

Chemical probes appended with reactive electrophiles afford powerful tools for profiling discrete protein families in living cells. Herein, we have synthesized cell-permeable chemical probes that target fatty acid-associated proteins. These fatty acid-based chemical probes contain acyloxymethylketone or fluorophosphonate functional groups and an alkyne click chemistry tag for visualization of covalently modified proteins by in-gel fluorescence scanning. Our fatty acid-based chemical probe affords new tools to evaluate the activity/expression of lipid-associated proteins that should facilitate their functional characterization and inhibitor discovery.