Quantitative Chemoproteomic Methods for Reactive Cysteinome Profiling

Abstract Reactive cysteines often serve as functional sites on proteins and play important regulatory roles in various biological processes. A chemoproteomic method named “isoTOP‐ABPP” has enabled global profiling of cysteine reactivity in native systems and greatly increased our understanding on reactive cysteinome. This elegant method and its derived chemoproteomic technologies are now widely applied in profiling of reactive cysteinome and the associated post‐translational modifications, discovery of covalent ligands for undruggable targets as well as mechanistic investigation of various biological processes. In this review, we will briefly go over the history of isoTOP‐ABPP, summarize recent developments and applications of chemoproteomic technology in reactive cysteinome profiling, and discuss future directions in this field.