Inorganic Polyhedral Metallacarborane Inhibitors of HIV Protease: A New Approach to Overcoming Antiviral Resistance

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...

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Veröffentlicht in:Journal of medicinal chemistry 2008-08, Vol.51 (15), p.4839-4843
Hauptverfasser: Kožíšek, Milan, Cígler, Petr, Lepšík, Martin, Fanfrlík, Jindřich, Řezáčová, Pavlína, Brynda, Jiří, Pokorná, Jana, Plešek, Jaromír, Grüner, Bohumír, Grantz Šašková, Klára, Václavíková, Jana, Král, Vladimír, Konvalinka, Jan
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Sprache:eng
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Zusammenfassung: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm8002334