The discovery of the protein targets of small molecule probes is a crucial aspect of activity-based protein profiling and chemical biology. Mass spectrometry is the primary method for target identification, and in the last decade, cleavable linkers have become a popular strategy to facilitate protein enrichment and identification. In this chapter, we provide an overview of cleavable linkers used in chemical proteomics approaches, discuss their different chemistries, and describe how they aid in protein identification.
Keywords: Activity-based probes; Chemical proteomics; Cleavable linkers; Click chemistry; Enrichment; Mass spectrometry; Protein identification; Target discovery.