Počet záznamů: 1
Specific Inhibitors of HIV Capsid Assembly Binding to the C-Terminal Domain of the Capsid Protein: Evaluation of 2-Arylquinazolines as Potential Antiviral Compounds
- 1.0458499 - ÚOCHB 2017 RIV US eng J - Článek v odborném periodiku
Machara, A. - Lux, V. - Kožíšek, Milan - Grantz Šašková, Klára - Štěpánek, O. - Kotora, M. - Parkan, Kamil - Pávová, Marcela - Glass, B. - Sehr, P. - Lewis, J. - Müller, B. - Kräusslich, H. G. - Konvalinka, Jan
Specific Inhibitors of HIV Capsid Assembly Binding to the C-Terminal Domain of the Capsid Protein: Evaluation of 2-Arylquinazolines as Potential Antiviral Compounds.
Journal of Medicinal Chemistry. Roč. 59, č. 2 (2016), s. 545-558. ISSN 0022-2623. E-ISSN 1520-4804
Grant CEP: GA ČR GA13-19561S
GRANT EU: European Commission(XE) 201095 - HIV ACE
Institucionální podpora: RVO:61388963
Klíčová slova: HIV-1 assembly * capsid * high-throughput screening * AlphaScreen assay
Kód oboru RIV: CE - Biochemie
Impakt faktor: 6.259, rok: 2016
Assembly of human immunodeficiency virus (HIV-1) represents an attractive target for antiretroviral therapy which is not exploited by currently available drugs. We established high-throughput screening for assembly inhibitors based on competition of small molecules for the binding of a known dodecapeptide assembly inhibitor to the C-terminal domain of HIV-1 CA (capsid). Screening of >70000 compounds from different libraries identified 2-arylquinazolines as low micromolecular inhibitors of HIV-1 capsid assembly. We prepared focused libraries of modified 2-arylquinazolines and tested their capacity to bind HIV-1 CA to compete with the known peptide inhibitor and to prevent the replication of HIV-1 in tissue culture. Some of the compounds showed potent binding to the C-terminal domain of CA and were found to block viral replication at low micromolar concentrations.
Trvalý link: http://hdl.handle.net/11104/0258765
Počet záznamů: 1