2010
[d4U]-Spacer-[HI-236] double-drug inhibitors of HIV-1 reverse-transcriptase
Younis Y, Hunter R, Muhanji C, Hale I, Singh R, Bailey C, Sullivan T, Anderson K. [d4U]-Spacer-[HI-236] double-drug inhibitors of HIV-1 reverse-transcriptase. Bioorganic & Medicinal Chemistry 2010, 18: 4661-4673. PMID: 20605472, PMCID: PMC2964380, DOI: 10.1016/j.bmc.2010.05.025.Peer-Reviewed Original Research
2008
C-2-Aryl O-substituted HI-236 derivatives as non-nucleoside HIV-1 reverse-transcriptase inhibitors
Hunter R, Younis Y, Muhanji C, Curtin T, Naidoo K, Petersen M, Bailey C, Basavapathruni A, Anderson K. C-2-Aryl O-substituted HI-236 derivatives as non-nucleoside HIV-1 reverse-transcriptase inhibitors. Bioorganic & Medicinal Chemistry 2008, 16: 10270-10280. PMID: 18996020, PMCID: PMC2639753, DOI: 10.1016/j.bmc.2008.10.048.Peer-Reviewed Original ResearchConceptsThiourea derivativesHI-236C-2 arylationC-2 oxygenStructure-activity profilePhenyl ringAnti-HIV activityNNRTI pocketC-2Drug designCell-free RT assaysDocking modelThioureaDerivativesInhibitory activityBifunctional inhibitorsImproved leadsPhenylAutoDockDockingRingCompoundsPocketSpatial characteristicsMT-2 cell cultures
2007
[d4U]-butyne-[HI-236] as a non-cleavable, bifunctional NRTI/NNRTI HIV-1 reverse-transcriptase inhibitor
Hunter R, Muhanji C, Hale I, Bailey C, Basavapathruni A, Anderson K. [d4U]-butyne-[HI-236] as a non-cleavable, bifunctional NRTI/NNRTI HIV-1 reverse-transcriptase inhibitor. Bioorganic & Medicinal Chemistry Letters 2007, 17: 2614-2617. PMID: 17317163, DOI: 10.1016/j.bmcl.2007.01.107.Peer-Reviewed Original Research
1996
HIV-1 Reverse Transcriptase Resistance to Nonnucleoside Inhibitors †
Spence R, Anderson K, Johnson K. HIV-1 Reverse Transcriptase Resistance to Nonnucleoside Inhibitors †. Biochemistry 1996, 35: 1054-1063. PMID: 8547241, DOI: 10.1021/bi952058+.Peer-Reviewed Original ResearchConceptsMutant enzymesPre-steady-state techniquesSingle nucleotide incorporationWild-type complexMaximum incorporation rateNucleotide incorporationEnzyme complexDuplex DNAAffinity 2Cysteine mutationsTwo-step bindingWild-typeConformational changesDecreased affinityEnzymePresence of nevirapineInhibitor resistanceMutationsIncorporation rateY181C mutationWild-type RTReverse transcriptaseHIV-1NevirapineY181C
1995
Mechanism of Inhibition of HIV-1 Reverse Transcriptase by Nonnucleoside Inhibitors
Spence R, Kati W, Anderson K, Johnson K. Mechanism of Inhibition of HIV-1 Reverse Transcriptase by Nonnucleoside Inhibitors. Science 1995, 267: 988-993. PMID: 7532321, PMCID: PMC7526747, DOI: 10.1126/science.7532321.Peer-Reviewed Original ResearchConceptsActive site catalytic residuesPre-steady-state kinetic analysisNucleotide-induced conformational changesInterfere with nucleotide bindingPre-steady-state burstEnzyme-DNA complexPre-steady-stateReverse transcriptasePresence of saturating concentrationsCatalytic residuesNucleotide bindingNucleoside triphosphatesDNA polymerizationNucleotide analogsHydrophobic pocketMechanism of inhibitionNonnucleoside inhibitorsConformational changesNoncompetitive inhibitorInhibition of HIV-1 reverse transcriptaseKinetic analysisHIV-1 reverse transcriptaseSaturating concentrationsTranscriptaseInhibitors