Abstract
HIV protease (PR) is a prime target for rational anti-HIV drug design. We have previously identified icosahedral metallacarboranes as a novel class of nonpeptidic protease inhibitors. Now we show that substituted metallacarboranes are potent and specific competitive inhibitors of drug-resistant HIV PRs prepared either by site-directed mutagenesis or cloned from HIV-positive patients. Molecular modeling explains the inhibition profile of metallacarboranes by their unconventional binding mode.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Boron Compounds / chemistry*
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Boron Compounds / pharmacology*
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Crystallography, X-Ray
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Drug Resistance, Viral / drug effects*
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HIV Protease / chemistry
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HIV Protease / genetics
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HIV Protease / metabolism*
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HIV Protease Inhibitors / chemistry*
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HIV Protease Inhibitors / pharmacology*
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HIV-1 / drug effects
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HIV-1 / enzymology
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Metals / chemistry*
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Models, Molecular
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Molecular Structure
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Mutation / genetics
Substances
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Boron Compounds
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HIV Protease Inhibitors
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Metals
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HIV Protease