Low-Toxicity Sulfonium-Based Probes for Cysteine-Specific Profiling in Live Cells

Despite being a low-abundance amino
acid, cysteine plays an essential
role in regulating protein function and serves as a satisfactory target
of post-translational modifications and drug developments. To comprehensively
assess reactive-cysteine-containing proteins, the development of chemical
proteomic probes to label cysteine residues in human cells is an important
objective. Cysteine modification using sulfonium-based probes is a
novel method to identify reactive cysteine residues in proteins. Herein,
we reported a set of “cysteine-reactive sulfonium-based (C-Sul)”
probes to label the reactive cysteine sites in cellular proteins.
Notably, water-soluble C-Sul probes have a significantly enhanced
stability and cellular uptakes, displaying a high specificity toward
reactive cysteines and compatibility with quantitative proteomic profiling.
In comparison to the conventional iodoacetamide-based probe, C-Sul
particularly has no inhibitory effects on cell viability, enabling
its application in proteomic profiling of reactive cysteine residues
under biorelevant conditions. We propose C-Sul probes as optimal tools
of cysteine profiling for further broadly basic research.