Abstract
Identifying the targets of bioactive compounds is often the rate limiting step toward understanding their mechanism of action. We have developed a novel photoreactive cleavable choloralkane tag that can be attached to bioactive compounds to isolate their respective cellular targets for identification by mass spectrometry. Following binding to the targets inside cells, UV-induced photo-crosslinking preserves the interactions with intracellular targets and enables efficient enrichment of those targets through their covalent capture onto HaloTag coated particle and subsequent selective release by tag cleavage. We will present studies demonstrating the capacity of this approach to identify the cellular targets of bioactive compounds including those with low affinity and/or low abundance.