Triketoacid inhibitors of HIV-integrase: A new chemotype useful for probing the integrase pharmacophore
| Autor: | Carol Deminie, Timothy Johnson, Oak K. Kim, Andrew J. Staab, Zeyu Lin, Roger Remillard, Brian Terry, Nicholas A. Meanwell, Mark Krystal, Michael A. Walker, Albert Torri, Jacques Banville, Henry Wong, Himadri Samanta, Zhuping Ma, Yunhui Zhang |
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| Rok vydání: | 2006 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Pharmaceutical Science HIV Integrase Biochemistry Structure-Activity Relationship Drug Discovery HIV Integrase Inhibitors Binding site Molecular Biology chemistry.chemical_classification Molecular Structure biology Chemotype Chemistry Organic Chemistry biology.organism_classification Nucleotidyltransferase Keto Acids Integrase Enzyme Enzyme inhibitor Lentivirus HIV-1 biology.protein Molecular Medicine Pharmacophore |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 16:2920-2924 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2006.03.010 |
| Popis: | Integrase is one of three enzymes expressed by HIV and represents a validated target for therapy. This study reports on the discovery of a new triketoacid-based chemotype that selectively inhibits the strand transfer reaction of HIV-integrase. SAR studies showed that the template binds to integrase in a manner similar to the diketoacid-based inhibitors. Moreover, comparison of the new chemotype to two different diketoacid templates led us to propose two aryl-binding domains in the inhibitor binding site. This information was used to design a new diketoacid template with improved activity against the enzyme. |
| Databáze: | OpenAIRE |
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