Activity-based proteomic profiling: The application of photoaffinity probes in the target identification of bioactive molecules

Identifying cellular targets for bioactive molecules is a major challenge and a key issue in drug discovery. Small molecule probes play an essential role in identifying targets of bioactive compounds. Photoaffinity labeling (PAL) has been developed as an emerging strategy owing to its capability of investigating the interaction between ligands and proteins. However, non-covalent interaction is too weak to precisely detect the target protein. PAL can covalently capture the target protein and offer a bioorthogonal reporter group to identify the target protein. Moreover, with its function in structural insight and instant binding site validation, PAL has the most potential to accelerate drug discovery. Herein, we will present an overview of the photoactive groups, reporter groups, and bio-orthogonal reactions involved in PAL, with a focus on their application in target identification of bioactive molecules. A number of comparative studies are described in which the efficiency of various photoaffinity probes are compared.