ArticleJournal of medicinal chemistry2011
Crystal structure of tert-butyldimethylsilyl-spiroaminooxathioledioxide-thymine (TSAO-T) in complex with HIV-1 reverse transcriptase (RT) redefines the elastic limits of the non-nucleoside inhibitor-binding pocket.
Article in Journal of medicinal chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Structural biology of HIV-1 reverse transcriptase allosteric inhibitors for drug design.Acta pharmaceutica Sinica. B · 2026Review
- Multicomponent Electrosynthesis of Enaminyl Sulfonates Starting from Alkylamines, SOOrganic letters · 2025Article
- Role of diosgenin extracted fromHeliyon · 2024Article
- Exploring the potential of some natural indoles as antiviral agents: quantum chemical analysis, inverse molecular docking, and affinity calculations.Frontiers in chemistry · 2024Article
- 5-Nitro-3-(2-(4-phenylthiazol-2-yl)hydrazineylidene)indolin-2-one derivatives inhibit HIV-1 replication by a multitarget mechanism of action.Frontiers in cellular and infection microbiology · 2023Article
- Effect of Selected Silyl Groups on the Anticancer Activity of 3,4-Dibromo-5-Hydroxy-Furan-2(5Pharmaceuticals (Basel, Switzerland) · 2021Article
- Exploring New Scaffolds for the Dual Inhibition of HIV-1 RT Polymerase and Ribonuclease Associated Functions.Molecules (Basel, Switzerland) · 2021Article
- Synthesis, study of antileishmanial and antitrypanosomal activity of imidazo pyridine fused triazole analogues.RSC advances · 2020Article
- Peptides Mimicking the β7/β8 Loop of HIV-1 Reverse Transcriptase p51 as "Hotspot-Targeted" Dimerization Inhibitors.ACS medicinal chemistry letters · 2020Article
- Improving the positional adaptability: structure-based design of biphenyl-substituted diaryltriazines as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.Acta pharmaceutica Sinica. B · 2020Article
- Structure of HIV-1 RT/dsRNA initiation complex prior to nucleotide incorporation.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- An integrated chemical biology approach reveals the mechanism of action of HIV replication inhibitors.Bioorganic & medicinal chemistry · 2017Article
- Isatin thiazoline hybrids as dual inhibitors of HIV-1 reverse transcriptase.Journal of enzyme inhibition and medicinal chemistry · 2017Article
- Structural Maturation of HIV-1 Reverse Transcriptase-A Metamorphic Solution to Genomic Instability.Viruses · 2016Review
- Rilpivirine analogs potently inhibit drug-resistant HIV-1 mutants.Retrovirology · 2016Article
- Article
- Computational drug design strategies applied to the modelling of human immunodeficiency virus-1 reverse transcriptase inhibitors.Memorias do Instituto Oswaldo Cruz · 2015Review
- Ligand similarity guided receptor selection enhances docking accuracy and recall for non-nucleoside HIV reverse transcriptase inhibitors.Journal of molecular modeling · 2015Article
- Probing the structural and molecular basis of nucleotide selectivity by human mitochondrial DNA polymerase γ.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Examining the role of the HIV-1 reverse transcriptase p51 subunit in positioning and hydrolysis of RNA/DNA hybrids.The Journal of biological chemistry · 2013Article
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8 authors.
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Abstract
tert-Butyldimethylsilyl-spiroaminooxathioledioxide (TSAO) compounds have an embedded thymidine-analogue backbone; however, TSAO compounds invoke non-nucleoside RT inhibitor (NNRTI) resistance mutations. Our crystal structure of RT:7 (TSAO-T) complex shows that 7 binds inside the NNRTI-binding pocket, assuming a "dragon" shape, and interacts extensively with almost all the pocket residues. The structure also explains the structure-activity relationships and resistance data for TSAO compounds. The binding of 7 causes hyper-expansion of the pocket and significant rearrangement of RT subdomains. This nonoptimal complex formation is apparently responsible (1) for the lower stability of a RT (p66/p51) dimer and (2) for the lower potency of 7 despite of its extensive interactions with RT. However, the HIV-1 RT:7 structure reveals novel design features such as (1) interactions with the conserved Tyr183 from the YMDD-motif and (2) a possible way for an NNRTI to reach the polymerase active site that may be exploited in designing new NNRTIs.
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