Bioorthogonal Probes for Analyzing Non‐Enzymatic Post‐Translational Modifications

Non‐enzymatic post‐translational modifications (nPTMs) have been proposed as indicators of cellular stresses and diseases. Unfortunately, direct assessment of nPTMs in native environment is extremely challenging due to the heterogeneity of adducts and the lack of tagging tools. Given these challenges, bioorthogonal probes (BPs) have been developed for the analysis of nPTMs. The rationality is that BPs could selectively install azides or alkynes into nPTMs as a biorthogonal handle for the following enrichment or tracking. Herein, we review the state‐of‐art of BPs used for nPTMs studies, clarify their working principles, and highlight how they advance our understanding of the biological functions of nPTMs. This review focuses on the development and application of bioorthogonal probes for the study of non‐enzymatic post‐translational modifications, which has been long time challenging due to the heterogeneity of adducts and the lack of appropriate tagging tools.