Probes for Photoaffinity Labeling of Kinases.

Protein kinases, one of the largest enzyme superfamilies, regulate many physiological and pathological processes. They are drug targets for multiple human diseases, including various cancer types. Probes for photoaffinity labeling of kinases represent important research tools for the study of members of this enzyme superfamily. In this review, we discuss the design principles of these probes, which are mainly derived from inhibitors targeting the ATP pocket. Overall, insights from crystal structures guide the placement of photoreactive groups and detection tags. This has resulted in a wide variety of probes, of which we provide a comprehensive overview. We also discuss several application areas of these probes, which include identification of targets and off-targets of kinase inhibitors, mapping of their binding sites, development of inhibitor screening assays, imaging of kinases, and identification of protein binding partners.