Synthetic Approaches of Epoxysuccinate Chemical Probes

Abstract Synthetic chemical probes are powerful tools for investigating biological processes. They are particularly useful for proteomic studies such as activity‐based protein profiling (ABPP). These chemical methods initially used mimics of natural substrates. As the techniques gained prominence, more and more elaborate chemical probes with increased specificity towards given enzyme/protein families and amenability to various reaction conditions were used. Among the chemical probes, peptidyl‐epoxysuccinates represent one of the first types of compounds used to investigate the activity of the cysteine protease papain‐like family of enzymes. Structurally derived from the natural substrate, a wide body of inhibitors and activity‐ or affinity‐based probes bearing the electrophilic oxirane unit for covalent labeling of active enzymes now exists. Herein, we review the literature regarding the synthetic approaches to epoxysuccinate‐based chemical probes together with their reported applications, from biological chemistry and inhibition studies to supramolecular chemistry and the formation of protein arrays.