A reactivity-based probe for off-on fluorescent detection, labeling, and profiling of protein S-sulfenylation in cells

Abstract

Protein S-sulfenylation modulates protein functions, redox homeostasis, various signaling pathways and cellular functions, and is thus associated with many diseases. However, the dynamic nature, transient fate of protein sulfenic acids, and the lack of probes which enable the spatial and temporal profiling of intracellular S-sulfenylation have hindered our understanding of this redox PTM. Herein, we reported a novel reaction of sulfenic acid towards arylhydrazine with high efficiency, and a multifunctional probe SA-HYD based on this reaction which enables “off-on” fluorescent detection, labeling and profiling of protein S-sulfenylation within cells. SA-HYD was applied successfully in “off-on” fluorescent imaging, in situ fluorescent labeling of intracellular protein sulfenic acids and LPA-mediated signaling research in prostate cancer cells. We expect this probe could provide a convenient and robust tool for better understanding the physiological and pathological roles of protein S-sulfenylation.