-Carbonyl sulfonium enables cysteine-specific bioconjugation for activity-based protein profiling in live cells

Chemical labeling methods for proteins are highly researched. Herein, we introduced beta-carbonyl sulfonium compounds for selective cysteine modification in proteins within biological systems. Structural tuning led to sulfonium-based probes with high reactivity and selectivity. These probes show excellent biocompatibility, cell uptake, and specificity towards cysteine profiling in live cells. Small electrophilic molecules have previously been reported to monitor different reactivities or covalent ligand abilities of nucleophilic residues in proteins. Herein, we develop beta-carbonyl sulfonium compounds to selectively modify cysteines in peptides and proteins in live cells.