RESUMO
Reported herein is a fluorescence assay for the rapid screening of metallo-ß-lactamase (MBL) inhibitors. This assay employs a fluorogenic carbapenem CPC-1 as substrate and is compatible with all MBLs, including B1, B2 and B3 subclass MBLs. The efficiency of this assay was demonstrated by the rapid inhibition screening of a number of molecules against B2 MBL CphA and 2,3-dimercaprol was identified as a potent CphA inhibitor.
Assuntos
Carbapenêmicos/química , Fluorescência , Corantes Fluorescentes/química , Inibidores de beta-Lactamases/química , Carbapenêmicos/farmacologia , Relação Dose-Resposta a Droga , Corantes Fluorescentes/farmacologia , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/metabolismoRESUMO
Reported herein is a relebactam-derived fluorogenic reagent for covalent labeling of serine ß-lactamases (SBLs), which are the major causes of bacterial resistance to ß-lactam antibiotics. This highly selective imaging reagent generates over 300-fold stronger near-infrared fluorescence signals upon covalently bonding to SBLs, allowing wash-free visualization of live antimicrobial-resistant bacteria.