Recent advances in chemical proteomics for protein profiling and targeted degradation.

Chemical proteomics has emerged as a powerful approach to decipher protein function, interactions, and targeted degradation pathways in complex biological systems. Recent advances in chemical labeling strategies, including activity-based protein profiling (ABPP), proximity labeling (PL), and proteolysis-targeting chimeras (PROTACs), have facilitated a deeper understanding of protein function and interaction networks. First, ABPP employs covalent probes to selectively label active enzymes, uncovering functional proteomics and drug-target interactions. Innovations such as PhosID-ABPP and streamlined cysteine ABPP have improved site-specific quantification and throughput, enabling proteome-wide analysis of enzyme activity and small-molecule interactions. Second, PL enables the characterization of transient protein-protein interactions using enzymatic or chemically triggered approaches. Advances including TurboID and TransitID enhanced the spatiotemporal resolution of PL. Third, PROTACs expand the scope of targeted protein degradation by leveraging the ubiquitin-proteasome system. Collectively, we highlight recent advancements in integrating mass spectrometry (MS) with these methodologies in the field of chemical proteomics.