S-sulfenylation is the oxidation of cysteine thiol (Cys-OH) to sulfenic acid (Cys-SOH) by a reactive oxygen species. This post-translational modification (PTM) plays a key role in the regulation of several protein functions including transcription factors, kinases, and ion channels. As a result of its role in biological systems, nucleophilic character, and oxidation susceptibility, cysteine thiols are primary targets for redox-based protein modulation. Previous work determined that carbon-centered nucleophilic probes are selective probes to label Cys-SOH modifications. In particular, fluorogenic probes reveal an increase in fluorescence upon binding to their targets, thus enabling detection of Cys-SOH modifications via cell imaging and high-throughput screening (HTS) applications. Development of these probes will enable their use on projects focused on altering or studying biological systems. Previously, our group developed a new class of fluorogenic probes (SNap1-2) that enabled visualization of Cys-SOH in live cells and identification of kinase inhibitors of which promote protein sulfenylation. We have recently used synthetic techniques to produce a new derivative, SNNO<sub>2</sub>, which showed improved fluorescence properties upon target binding compared to previous derivatives. The improvement in fluorescence will also enable further application of these specific probes in biological systems other than kinases and allow the manipulation of cysteine thiols and S-sulfenylation within their research.

Fluorogenic probes for the elucidation of cysteine oxidation

ACS Spring 2022

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