Article

A Novel Pharmacophore Model for the Design of Anthrax Lethal Factor Inhibitors

Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Chemical Biology &amp Drug Design (Impact Factor: 2.51). 09/2010; 76(3):263-8. DOI: 10.1111/j.1747-0285.2010.01000.x
Source: PubMed

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.

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Available from: Sherida L Johnson, Jun 11, 2014
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