RESUMO
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.
Assuntos
Marcadores de Afinidade/farmacologia , Compostos Azabicíclicos/farmacologia , Enterobacter cloacae/isolamento & purificação , Corantes Fluorescentes/farmacologia , Inibidores de beta-Lactamases/farmacologia , beta-Lactamases/química , Marcadores de Afinidade/síntese química , Marcadores de Afinidade/química , Compostos Azabicíclicos/síntese química , Compostos Azabicíclicos/química , Enterobacter cloacae/enzimologia , Fluoresceínas/síntese química , Fluoresceínas/química , Fluoresceínas/farmacologia , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Indóis/síntese química , Indóis/química , Indóis/farmacologia , Inibidores de beta-Lactamases/síntese química , Inibidores de beta-Lactamases/químicaRESUMO
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.
