Reactive Chemical Probes: Beyond the Kinase Cysteinome

The reaction of small-molecule chemical probes with proteins has been harnessed to develop covalent inhibitor drugs and protein-profiling technologies. This Essay discusses some of the recent enhancements to the chemical biology toolkit that are enabling the study of previously unchartered areas of chemoproteomic space. An analysis of the kinome is used to illustrate the potential for these approaches enable the pursuit of new targets using reactive chemical probes.