A protein structure-guided covalent scaffold selectively targets the B1 and B2 subclass metallo-β-lactamases.

We report the discovery of ebselen-based dual covalent inhibitors of metallo-β-lactamases. Fluorescence and MALDI-TOF analysis suggested that the scaffold could bind to NDM-1 by forming a S-Se bond with Cys221 and an amide bond with Lys224 of NDM-1, thereby exhibiting selective inhibition and labeling against B1 and B2 subclass enzymes in vitro and in vivo.