Synthetic approaches of epoxysuccinate chemical probes.

Abstract

Synthetic chemical probes are powerful tools for investigation of 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 elaborated chemical probes with increased specificity towards given enzyme/protein families and amenability to various reaction conditions have been used. Among chemical probes, peptidyl-epoxysuccinates represent one of the first type of compounds used to investigate activity of cysteine proteases papain-like family of enzymes. Structurally derived from the natural substrate to date exists a wide body of inhibitors and activity- or affinity-based probes bearing the electrophilic oxirane unit for covalent labelling of active enzymes. Herein we review the literature regarding the synthetic approaches to epoxysuccinate-based chemical probes together with the reported applications, from biological chemistry and inhibition studies to supramolecular chemistry and formation of protein arrays.