Cyclic boronates as versatile scaffolds for KPC-2 β-lactamase inhibition
Catherine L. Tooke, Philip Hinchliffe, Alen Krajnc, Adrian J. Mulholland, Jürgen Brem, Christopher J. Schofield, James Spencer
Abstract
. High resolution X-ray crystal structures reveal closely related binding modes for both inhibitors to KPC-2, with differences apparent only in positioning of the endocyclic boronate ester oxygen. The results indicate the bicyclic boronate scaffold as both an efficient, long-lasting, KPC-2 inhibitor and capable of supporting further iterations that may improve potency against specific enzyme targets and pre-empt the emergence of inhibitor resistant KPC-2 variants.
Topics & Concepts
Klebsiella pneumoniaeBicyclic moleculeSerineStereochemistryChemistryAntibioticsLactamPet imagingEnzymePharmacologyBiologyBiochemistryPositron emission tomographyEscherichia coliGeneNeuroscienceAntibiotic Resistance in BacteriaPneumocystis jirovecii pneumonia detection and treatmentAntibiotics Pharmacokinetics and Efficacy