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

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

  • Anal Chem. 2022 Mar 15;94(10):4366-4372. doi: 10.1021/acs.analchem.1c05129.
Rui Wang 1 Dongyan Yang 2 Tian Tian 3 4 Yuhao An 1 Chuan Wan 5 Qi Chang 1 Mingchan Liang 1 Zhanfeng Hou 1 Ying Wang 3 4 Liang Zhang 3 4 Zigang Li 5 1
Affiliations

Affiliations

  • 1 Pingshan Translational Medicine Center, Shenzhen Bay Laboratory, Shenzhen 518118, PR China.
  • 2 Innovative Institute for Plant Health, College of Chemistry and Chemical Engineering, Zhongkai University of Agriculture and Engineering, Guangzhou 510225, PR China.
  • 3 Key Laboratory of Biochip Technology, Biotech and Health Centre, Shenzhen Research Institute of City University of Hong Kong, Shenzhen 518057, PR China.
  • 4 Department of Biomedical Sciences, College of Veterinary Medicine and Life Sciences, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong 999077, PR China.
  • 5 State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen 518055, PR China.
Abstract

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.

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