Inorganic Polyhedral Metallacarborane Inhibitors of HIV Protease: A New Approach to Overcoming Antiviral Resistance
| Autor: | Klára Grantz Šašková, Jan Konvalinka, Jana Václavíková, Jiri Brynda, Jaromír Plešek, Martin Lepšík, Bohumír Grüner, Milan Kozisek, Vladimír Král, Pavlina Rezacova, Petr Cigler, Jana Pokorná, Jindrich Fanfrlík |
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| Rok vydání: | 2008 |
| Předmět: |
Boron Compounds
Models Molecular Molecular model Stereochemistry medicine.medical_treatment Mutagenesis (molecular biology technique) Crystallography X-Ray Virus HIV Protease Drug Resistance Viral Drug Discovery medicine Protease inhibitor (pharmacology) chemistry.chemical_classification Protease Molecular Structure biology virus diseases Biological activity HIV Protease Inhibitors Enzyme chemistry Biochemistry Metals Enzyme inhibitor Mutation HIV-1 biology.protein Molecular Medicine |
| Zdroj: | Journal of Medicinal Chemistry. 51:4839-4843 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm8002334 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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