Drug discovery today, 2015-04, Vol.20 (4), p.435-449
2015
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- Autor(en) / Beteiligte
- Titel
- Targeting HIV-1 integrase with strand transfer inhibitors
- Ist Teil von
- Drug discovery today, 2015-04, Vol.20 (4), p.435-449
- Ort / Verlag
- England: Elsevier Ltd
- Erscheinungsjahr
- 2015
- Quelle
- Access via ScienceDirect (Elsevier)
- Beschreibungen/Notizen
- •Overview of structural and functional properties of HIV-1 integrase (IN).•Classifying the HIV-1 integrase strand transfer inhibitors (INSTIs) into ten classes.•Summarizing the essential features and the development of HIV-1 INSTIs. HIV-1 integrase (IN) is a retroviral enzyme essential for integration of genetic material into the DNA of the host cell and hence for viral replication. The absence of an equivalent enzyme in humans makes IN an interesting target for anti-HIV drug design. This review briefly overviews the structural and functional properties of HIV-1 IN. We analyze the binding modes of the established drugs, clinical candidates and a comprehensive library of leads based on innovative chemical scaffolds of HIV-1 IN strand transfer inhibitors (INSTIs). Computational clustering techniques are applied for identifying structural features relating to bioactivity. From bio- and chemo-informatics analyses, we provide novel insights into structure–activity relationships of INSTIs and elaborate new strategies for design of innovative inhibitors. This review summarizes the structural and functional properties of HIV-1 integrase, the hot-spot active site and investigates the relationship between molecular scaffolds and activity of strand transfer inhibitors.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1359-6446eISSN: 1878-5832DOI: 10.1016/j.drudis.2014.12.001Titel-ID: cdi_proquest_miscellaneous_1691602222
- Format
- –
- Schlagworte
- Animals, Anti-HIV Agents - chemistry, Anti-HIV Agents - metabolism, Anti-HIV Agents - pharmacology, Binding Sites, Catalytic Domain, Cluster Analysis, Computational Biology, Computer-Aided Design, Drug Design, HIV Integrase - chemistry, HIV Integrase - metabolism, HIV Integrase Inhibitors - chemistry, HIV Integrase Inhibitors - metabolism, HIV Integrase Inhibitors - pharmacology, HIV-1 - drug effects, HIV-1 - enzymology, Humans, Ligands, Models, Molecular, Molecular Targeted Therapy, Protein Binding, Protein Conformation, Structure-Activity Relationship