Inorganic Polyhedral Metallacarborane Inhibitors of HIV Protease: A New Approach to Overcoming Antiviral Resistance
Journal of Medicinal Chemistry2008Vol. 51(15), pp. 4839–4843
Citations Over TimeTop 10% of 2008 papers
Milan Kožíšek, Petr Cígler, Martin Lepšı́k, Jindřich Fanfrlík, Pavlína Řezáčová, J. Brynda, Jana Pokorná, J. Plešek, Bohumı́r Grüner, Klára Grantz Šašková, Jana Václavíková, Vladimı́r Král, Jan Konvalinka
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.
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