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Updated: Aug 6, 2026

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Published on: June 21, 2021
Redox-activated chemistry for probing and perturbing the proteome: Lessons from protein redox switches
Qiyue Zeng1, Jingcheng Yang1, Dan He1
1School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore.
Abstract:
Covalent drug discovery and chemical proteomics have historically relied on a nucleophilic logic, where electrophilic "warheads" react with nucleophilic amino acid side chains. While powerful, this paradigm probes only a single dimension of the protein's chemical surface. In contrast, biology leverages a second axis: redox potential. This is exemplified by the regulated redox proteome, where specific residues undergo reversible oxidation and reduction as functional post-translational modifications. Inspired by this natural machinery, researchers are developing redox-activated probes to label proteins at oxidizable residues and deploying similar chemistry to selectively perturb protein function. This review highlights recent advances in redox-activated covalent chemistry and explores its burgeoning potential for the development of next-generation targeted therapeutics.
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