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.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Antigens, Bacterial
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Bacillus anthracis / enzymology*
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Bacterial Toxins / antagonists & inhibitors*
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Crystallography, X-Ray
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Metalloendopeptidases / antagonists & inhibitors*
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Models, Molecular
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Molecular Structure
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Protease Inhibitors* / chemical synthesis
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Protease Inhibitors* / chemistry
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Protease Inhibitors* / pharmacology
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Rhodanine* / analogs & derivatives
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Rhodanine* / chemical synthesis
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Rhodanine* / pharmacology
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Structure-Activity Relationship
Substances
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Antigens, Bacterial
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Bacterial Toxins
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Protease Inhibitors
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anthrax toxin
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Rhodanine
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Metalloendopeptidases