title: Inorganic polyhedral metallacarborane inhibitors of HIV protease: a new approach to overcoming antiviral resistance.
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.
authors.affiliation: Gilead Sciences and IOCB Research Center Prague, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Praha, Czech Republic.
authors.forename: Milan
authors.initials: M
authors.lastname: Kozísek
authors.forename: Petr
authors.initials: P
authors.lastname: Cígler
authors.forename: Martin
authors.initials: M
authors.lastname: Lepsík
authors.forename: Jindrich
authors.initials: J
authors.lastname: Fanfrlík
authors.forename: Pavlína
authors.initials: P
authors.lastname: Rezácová
authors.forename: Jirí
authors.initials: J
authors.lastname: Brynda
authors.forename: Jana
authors.initials: J
authors.lastname: Pokorná
authors.forename: Jaromír
authors.initials: J
authors.lastname: Plesek
authors.forename: Bohumír
authors.initials: B
authors.lastname: Grüner
authors.forename: Klára
authors.initials: K
authors.lastname: Grantz Sasková
authors.forename: Jana
authors.initials: J
authors.lastname: Václavíková
authors.forename: Vladimír
authors.initials: V
authors.lastname: Král
authors.forename: Jan
authors.initials: J
authors.lastname: Konvalinka
mesh_terms: D001896:Boron Compounds / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D024882:Drug Resistance, Viral / Q000187:drug effects*; D016333:HIV Protease / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D008670:Metals / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation / Q000235:genetics
chemical_list: D001896:Boron Compounds; D017320:HIV Protease Inhibitors; D008670:Metals; D016333:HIV Protease