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A Novel Pharmacophore Model for the Design of Anthrax Lethal Factor Inhibitors
Article first published online: 21 JUN 2010
DOI: 10.1111/j.1747-0285.2010.01000.x
© 2010 John Wiley & Sons A/S
1747-0285/asset/cover.gif?v=1&s=8fe4d6b0c02f69b0a8e26559215766f940e07347 "Chemical Biology & Drug Design")
Additional Information
How to Cite
Yuan, H., Johnson, S. L., Chen, L.-H., Wei, J. and Pellecchia, M. (2010), A Novel Pharmacophore Model for the Design of Anthrax Lethal Factor Inhibitors. Chemical Biology & Drug Design, 76: 263–268. doi: 10.1111/j.1747-0285.2010.01000.x
Publication History
- Issue published online: 2 AUG 2010
- Article first published online: 21 JUN 2010
- Received 18 March 2010, revised 19 May 2010 and accepted for publication 26 May 2010
- Abstract
- Article
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- Cited By
Keywords:
- Anthrax;
- drug design;
- LF;
- Pharmacophore
This study aims at the identification of novel structural features on the surface of the Zn-dependant 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.