My lab’s interest in boron-containing compounds has led to a sustained exploration of electrophiles that engage nucleophilic residues in proteins. In contrast to aldehydes, acrylates and epoxides, which are widely used as “baits” for nucleophilic residues in active sites, small boron-containing electrophiles have received relatively little attention. This is mainly due to their lack of stability and relative difficulty of preparation, especially when it comes to molecules with C(sp3)-B bonds. Over the past year or so, we have been working together with Ben Cravatt of the Scripps Research Institute, trying to get off the ground a research program aimed at “borofragments”. Our first paper just came out in Chem. Comm. In it, we describe a reagent that enables straightforward linking of biologically relevant heterocycles with boron. The stability of our molecules depends on the MIDA group, which acts as a slow-release element under biological conditions. This group stabilizes borofragments against premature decomposition and is released under biological conditions to unmask an active boronic acid. Borofragments can be used to discover inhibitors of enzymes that use catalytic oxygen nucleophiles. We have resorted to Ben’s activity-based protein profiling and employed our method to identify inhibitors of ABHD10 and the predicted carboxypeptidase CPVL. This technique should be applicable to other classes of targets. Given the diversity of heterocycles that are either commercially available or exist in the historical collections of the pharmaceutical industry, our straightforward method of linking molecular recognition units with stabilized boron electrophiles should enable facile exploration of previously uncharted covalent inhibitor space. I really have to thank my Japanese co-worker, Dr. Shinya Adachi, for developing this useful chemistry.