Discovery of Heteroaromatic Sulfones As a New Class of Biologically Compatible Thiol-Selective Reagents

• Published in: ACS chemical biology Vol. 12; no. 8; pp. 2201 - 2208
• Main Authors: Chen, Xiaofei, Wu, Hanzhi, Park, Chung-Min, Poole, Thomas H, Keceli, Gizem, Devarie-Baez, Nelmi O, Tsang, Allen W, Lowther, W. Todd, Poole, Leslie B, King, S. Bruce, Xian, Ming, Furdui, Cristina M
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18.08.2017
• Subjects: Cell Line, Tumor; Cell Membrane - drug effects; Drug Discovery; Humans; Mass Spectrometry; Models, Biological; Molecular Structure; Phenols - chemistry; Sulfhydryl Reagents - chemistry; Sulfhydryl Reagents - pharmacokinetics; Sulfhydryl Reagents - pharmacology; Sulfones - chemistry; Sulfones - pharmacokinetics; Sulfones - pharmacology; Tetrazoles - chemistry
• ISSN: 1554-8929; 1554-8937
• DOI: 10.1021/acschembio.7b00444

The selective reaction of chemical reagents with reduced protein thiols is critical to biological research. This reaction is utilized to prevent cross-linking of cysteine-containing peptides in common proteomics workflows and is applied widely in discovery and targeted redox investigations of the mechanisms underlying physiological and pathological processes. However, known and commonly used thiol blocking reagents like iodoacetamide, N-ethylmaleimide, and others were found to cross-react with oxidized protein sulfenic acids (−SOH) introducing significant errors in studies employing these reagents. We have investigated and are reporting here a new heteroaromatic alkylsulfone, 4-(5-methanesulfonyl-[1,2,3,4]­tetrazol-1-yl)-phenol (MSTP), as a selective and highly reactive −SH blocking reagent compatible with biological applications.