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A novel pharmacophore model for the design of anthrax lethal factor inhibitors.

ABSTRACT: This study aims at the identification of novel structural features on the surface of the Zn-dependent metalloprotease lethal factor (LF) from anthrax onto which to design novel and selective inhibitors. We report that by targeting an unexplored region of LF that exhibits ligand-induced conformational changes, we could obtain inhibitors with at least 30-fold LF selectivity compared to two other most related human metalloproteases, MMP-2 and MMP-9. Based on these results, we propose a novel pharmacophore model that, together with the preliminarily identified compounds, should help the design of more potent and selective inhibitors against anthrax.

SUBMITTER: Yuan H

PROVIDER: S-EPMC2918674 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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A novel pharmacophore model for the design of anthrax lethal factor inhibitors.

Yuan Hongbin H Johnson Sherida L SL Chen Li-Hsing LH Wei Jun J Pellecchia Maurizio M

Chemical biology & drug design 20100621 3

This study aims at the identification of novel structural features on the surface of the Zn-dependent metalloprotease lethal factor (LF) from anthrax onto which to design novel and selective inhibitors. We report that by targeting an unexplored region of LF that exhibits ligand-induced conformational changes, we could obtain inhibitors with at least 30-fold LF selectivity compared to two other most related human metalloproteases, MMP-2 and MMP-9. Based on these results, we propose a novel pharma ...[more]

PMID: 20572812

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