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Letter

Anthrax Lethal Factor Protease Inhibitors: Synthesis, SAR, and Structure-Based 3D QSAR Studies

Supporting Info

Sherida L. Johnson,^† Dawoon Jung,^† Martino Forino,^‡ Ya Chen, Arnold Satterthwait, Dmitry V. Rozanov, Alex Y. Strongin, and Maurizio Pellecchia*

Cancer Research Center and Infectious and Inflammatory Disease Center, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, California 92037

J. Med. Chem., 2006, 49 (1), pp 27–30

DOI: 10.1021/jm050892j

Publication Date (Web): December 1, 2005

†

These authors contributed equally to this work.

‡

Present address: Dipartimento di Chimica delle Sostanze Naturali, Facoltà di Farmacia, Università degli Studi “Federico II” di Napoli, Italy.

To whom correspondence should be addressed. Tel: (858) 646-3159. Fax: (858) 713-9925. E-mail: mpellecchia@burnham.org.

Abstract

We have recently identified a series of compounds that efficiently inhibit anthrax lethal factor (LF) metallo-protease. Here we present further structure−activity relationship and CoMFA (comparative molecular field analysis) studies on newly derived inhibitors. The obtained 3D QSAR model was subsequently compared with the X-ray structure of the complex between LF and a representative compound. Our studies form the basis for the rational design of additional compounds with improved activity and selectivity.

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PDB: 1ZXV

History

Published In Issue January 12, 2006
Received September 9, 2005

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Letter

Anthrax Lethal Factor Protease Inhibitors: Synthesis, SAR, and Structure-Based 3D QSAR Studies

Abstract

Tools

SciFinder Links

Accession Codes

History

Recommend & Share

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Discovery of Nonpeptidic Small-Molecule AP-1 Inhibitors: Lead Hopping Based on a Three-Dimensional Pharmacophore Model

Molecular Dynamics Simulations of Ligand Dissociation from Thyroid Hormone Receptors: Evidence of the Likeliest Escape Pathway and Its Implications for the Design of Novel Ligands

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