Ebselen as a potent covalent inhibitor of New Delhi metallo-β-lactamase (NDM-1)

Jiachi Chiou(Hong Kong Polytechnic University), Shengbiao Wan(Ministry of Education), Kin‐Fai Chan(Hong Kong Polytechnic University), Pui‐Kin So(Hong Kong Polytechnic University), Dandan He(Hong Kong Polytechnic University), Edward Wai‐Chi Chan(Hong Kong Polytechnic University), Tak Hang Chan(Hong Kong Polytechnic University), Kwok‐Yin Wong(Hong Kong Polytechnic University), Tao Jiang(Ministry of Education), Sheng Chen(Hong Kong Polytechnic University)
Chemical Communications
January 1, 2015
Cited by 134

Abstract

We report the discovery of a promising NDM-1 inhibitor, ebselen, through a cell-based screening approach. Enzymatic kinetic study and ESI-MS analysis suggested that ebselen could bind to NDM-1 by forming a S-Se bond with the Cys(221) residue at the active site, thereby exhibiting a new inhibition mechanism with broad spectrum inhibitory potential.


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