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

作者：Wang, Rui; Yang, Dongyan; Tian, Tian; An, Yuhao; Wan, Chuan; Chang, Qi; Liang, Mingchan; Hou, Zhanfeng; Wang, Ying; Zhang, Liang^*; Li, Zigang^*

来源：Analytical Chemistry, 2022, 94(10): 4366-4372.

DOI：10.1021/acs.analchem.1c05129

• CYCLOADDITION
• MOLECULES

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.

• 单位
  仲恺农业工程学院; 北京大学