2023
Exploring novel HIV‐1 reverse transcriptase inhibitors with drug‐resistant mutants: A double mutant surprise
Hollander K, Chan A, Frey K, Hunker O, Ippolito J, Spasov K, Yeh Y, Jorgensen W, Ho Y, Anderson K. Exploring novel HIV‐1 reverse transcriptase inhibitors with drug‐resistant mutants: A double mutant surprise. Protein Science 2023, 32: e4814. PMID: 37861472, PMCID: PMC10659932, DOI: 10.1002/pro.4814.Peer-Reviewed Original ResearchConceptsHIV drug developmentReverse transcriptaseHIV-1 reverse transcriptaseNew RT inhibitorsDrug-resistant mutantsLifelong treatmentHIV-1 reverseRT inhibitorsClinical isolatesPreclinical candidateResistance mutationsResistant variantsSuccessful managementMolecular cloneFirst-generation inhibitorsDrug developmentV106ASame mutationCandidate compoundsGeneration inhibitorsInhibitorsKey targetCatechol diethersCovalent and noncovalent strategies for targeting Lys102 in HIV-1 reverse transcriptase
Prucha G, Henry S, Hollander K, Carter Z, Spasov K, Jorgensen W, Anderson K. Covalent and noncovalent strategies for targeting Lys102 in HIV-1 reverse transcriptase. European Journal Of Medicinal Chemistry 2023, 262: 115894. PMID: 37883896, PMCID: PMC10872499, DOI: 10.1016/j.ejmech.2023.115894.Peer-Reviewed Original ResearchDesign, synthesis, and biological testing of biphenylmethyloxazole inhibitors targeting HIV-1 reverse transcriptase
Carter Z, Hollander K, Spasov K, Anderson K, Jorgensen W. Design, synthesis, and biological testing of biphenylmethyloxazole inhibitors targeting HIV-1 reverse transcriptase. Bioorganic & Medicinal Chemistry Letters 2023, 84: 129216. PMID: 36871704, PMCID: PMC10278203, DOI: 10.1016/j.bmcl.2023.129216.Peer-Reviewed Original Research
2014
Recent Findings on the Mechanisms Involved in Tenofovir Resistance
Iyidogan P, Anderson K. Recent Findings on the Mechanisms Involved in Tenofovir Resistance. Antiviral Chemistry And Chemotherapy 2014, 23: 217-222. PMID: 23744599, PMCID: PMC4077986, DOI: 10.3851/imp2628.Peer-Reviewed Original ResearchMeSH KeywordsAdenineAlkynesAnti-HIV AgentsBenzoxazinesCyclopropanesDrug Resistance, ViralDrug SynergismHIV-1OrganophosphonatesTenofovirConceptsReverse transcriptase inhibitorsDrug resistanceResistance mechanismsNon-nucleoside reverse transcriptase inhibitorsHIV-1 infectionLong-term efficacyMechanism of RTSynergistic antiviral effectTenofovir resistanceAntiretroviral agentsCombination therapyTreatment failureAntiviral synergySafety profileTranscriptase inhibitorsHIV-1TenofovirClinical useAntiviral effectTherapyViral sequencesNucleotide analoguesRegimensEfavirenzCurrent Perspectives on HIV-1 Antiretroviral Drug Resistance
Iyidogan P, Anderson K. Current Perspectives on HIV-1 Antiretroviral Drug Resistance. Viruses 2014, 6: 4095-4139. PMID: 25341668, PMCID: PMC4213579, DOI: 10.3390/v6104095.Peer-Reviewed Original ResearchMeSH KeywordsAnti-HIV AgentsAnti-Retroviral AgentsDrug Resistance, ViralHIV InfectionsHIV-1HumansMutagenesis
2012
Pre-steady state kinetic analysis of cyclobutyl derivatives of 2′-deoxyadenosine 5′-triphosphate as inhibitors of HIV-1 reverse transcriptase
Kim J, Wang L, Li Y, Becnel K, Frey K, Garforth S, Prasad V, Schinazi R, Liotta D, Anderson K. Pre-steady state kinetic analysis of cyclobutyl derivatives of 2′-deoxyadenosine 5′-triphosphate as inhibitors of HIV-1 reverse transcriptase. Bioorganic & Medicinal Chemistry Letters 2012, 22: 4064-4067. PMID: 22595174, PMCID: PMC3362660, DOI: 10.1016/j.bmcl.2012.04.078.Peer-Reviewed Original ResearchBalancing Antiviral Potency and Host Toxicity: Identifying a Nucleotide Inhibitor with an Optimal Kinetic Phenotype for HIV-1 Reverse Transcriptase
Sohl C, Kasiviswanathan R, Kim J, Pradere U, Schinazi R, Copeland W, Mitsuya H, Baba M, Anderson K. Balancing Antiviral Potency and Host Toxicity: Identifying a Nucleotide Inhibitor with an Optimal Kinetic Phenotype for HIV-1 Reverse Transcriptase. Molecular Pharmacology 2012, 82: 125-133. PMID: 22513406, PMCID: PMC3382833, DOI: 10.1124/mol.112.078758.Peer-Reviewed Original ResearchConceptsNucleoside reverse transcriptase inhibitorsHost toxicityClinical trialsReverse transcriptaseTreatment of HIV infectionMinimal host toxicityUnique toxicity profilePhase II clinical trialReverse transcriptase inhibitorsII clinical trialsHIV-1 reverse transcriptaseWild-typeAntiretroviral efficacyHIV infectionToxicity profileTranscriptase inhibitorsHIV-1Molecular mechanismsTreat HIVMechanisms of toxicityMitochondrial toxicityMolecular mechanisms of toxicityAntiviral potencyViral target proteinsThymidine analog
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
2006
Developing novel nonnucleoside HIV-1 reverse transcriptase inhibitors: beyond the butterfly.
Basavapathruni A, Anderson K. Developing novel nonnucleoside HIV-1 reverse transcriptase inhibitors: beyond the butterfly. Current Pharmaceutical Design 2006, 12: 1857-65. PMID: 16724952, DOI: 10.2174/138161206776873617.Peer-Reviewed Original ResearchConceptsNonnucleoside reverse transcriptase inhibitorsReverse transcriptase inhibitorsTranscriptase inhibitorsHuman immunodeficiency virus type 1 infectionResistance to nonnucleoside reverse transcriptase inhibitorsTreatment of human immunodeficiency virus type 1 infectionType 1 infectionFood and Drug AdministrationU.S. Food and Drug AdministrationCombination therapyDevelopment of resistanceMechanism of actionHIV-1 reverse transcriptase inhibitorsDrug AdministrationNonnucleosideNonnucleoside HIV-1 reverse transcriptase inhibitorNonnucleoside inhibitorsFeatures of inhibitionPotential new inhibitorsInhibitorsAmino acid substitutionsBiochemical featuresMolecular mechanismsNew inhibitorsAcid substitutions
2001
Deoxythioguanosine triphosphate impairs HIV replication: a new mechanism for an old drug
KRYNETSKAIA N, FENG J, KRYNETSKI E, GARCIA J, PANETTA J, ANDERSON K, EVANS W. Deoxythioguanosine triphosphate impairs HIV replication: a new mechanism for an old drug. The FASEB Journal 2001, 15: 1902-1908. PMID: 11532970, DOI: 10.1096/fj.01-0124com.Peer-Reviewed Original ResearchConceptsAnti-retroviral agentsHIV replicationHIV-1 reverse transcriptaseReverse transcriptaseTreatment of HIVHuman lymphocyte culturesDifferent medicationsHost lymphocytesAdditive cytotoxicityHIV-1Old drugsLymphocyte culturesActive metaboliteHuman lymphocytesMinimal toxicityLymphocytesThioguanineSubstantial inhibitionTreatmentInhibitionHIV proteaseEarly stagesMedicationsHIVPatientsInsights into the Molecular Mechanism of Mitochondrial Toxicity by AIDS Drugs*
Feng J, Johnson A, Johnson K, Anderson K. Insights into the Molecular Mechanism of Mitochondrial Toxicity by AIDS Drugs*. Journal Of Biological Chemistry 2001, 276: 23832-23837. PMID: 11328813, DOI: 10.1074/jbc.m101156200.Peer-Reviewed Original ResearchMeSH KeywordsAcquired Immunodeficiency SyndromeAnti-HIV AgentsCytidine TriphosphateDeoxycytosine NucleotidesDideoxynucleotidesDNADNA Polymerase gammaDNA ReplicationDNA, MitochondrialDNA-Directed DNA PolymeraseExodeoxyribonucleasesHumansKineticsLamivudineMitochondriaNucleic Acid Synthesis InhibitorsReverse Transcriptase InhibitorsZalcitabineConceptsPol gammaHuman mitochondrial DNA polymeraseHuman pol gammaMitochondrial DNA replicationMitochondrial DNA polymeraseToxicity of nucleoside analogsCytosine analogsMechanism of mitochondrial toxicityExonuclease activityDNA primersDNA replicationDNA polymeraseNucleoside analogsRate of excisionStructure/function relationshipsMolecular mechanismsLong-term administrationToxic inhibitorsExonucleaseTreatment of AIDSPolymeraseClinical toxicityMitochondrial toxicityDNAPolMECHANISTIC STUDIES TO UNDERSTAND THE INHIBITION OF WILD TYPE AND MUTANT HIV-1 REVERSE TRANSCRIPTASE BY CARBOVIR-TRIPHOSPHATE
Ray A, Anderson K. MECHANISTIC STUDIES TO UNDERSTAND THE INHIBITION OF WILD TYPE AND MUTANT HIV-1 REVERSE TRANSCRIPTASE BY CARBOVIR-TRIPHOSPHATE. Nucleosides Nucleotides & Nucleic Acids 2001, 20: 1247-1250. PMID: 11562995, DOI: 10.1081/ncn-100002528.Peer-Reviewed Original ResearchMechanism of Action of 1-β-d-2,6-Diaminopurine Dioxolane, a Prodrug of the Human Immunodeficiency Virus Type 1 Inhibitor 1-β-d-Dioxolane Guanosine
Furman P, Jeffrey J, Kiefer L, Feng J, Anderson K, Borroto-Esoda K, Hill E, Copeland W, Chu C, Sommadossi J, Liberman I, Schinazi R, Painter G. Mechanism of Action of 1-β-d-2,6-Diaminopurine Dioxolane, a Prodrug of the Human Immunodeficiency Virus Type 1 Inhibitor 1-β-d-Dioxolane Guanosine. Antimicrobial Agents And Chemotherapy 2001, 45: 158-165. PMID: 11120959, PMCID: PMC90254, DOI: 10.1128/aac.45.1.158-165.2001.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine Deaminase InhibitorsAnti-HIV AgentsBone Marrow CellsCells, CulturedDioxolanesDNA, ViralDrug Resistance, MicrobialEnzyme InhibitorsGuanosineHIV-1HumansLactic AcidMicroscopy, ElectronMitochondriaNucleic Acid Synthesis InhibitorsProdrugsPurine NucleosidesReverse Transcriptase InhibitorsConceptsDiaminopurine dioxolaneDXG-TPNucleoside reverse transcriptase inhibitorHuman immunodeficiency virus type 1Peripheral blood mononuclear cellsImmunodeficiency virus type 1Blood mononuclear cellsReverse transcriptase inhibitorAdenosine deaminaseVirus type 1Alternative substrate inhibitorsHIV-1 RTMechanism of actionWater-soluble prodrugMononuclear cellsDioxolane guanosineTranscriptase inhibitorType 1CEM cellsInhibitor-1Mitochondrial toxicityHuman DNA polymerase alphaCalf adenosine deaminaseInhibitorsDNA polymerase gamma
2000
An analysis of the catalytic cycle of HIV-1 reverse transcriptase: opportunities for chemotherapeutic intervention based on enzyme inhibition.
Furman P, Painter G, Anderson K. An analysis of the catalytic cycle of HIV-1 reverse transcriptase: opportunities for chemotherapeutic intervention based on enzyme inhibition. Current Pharmaceutical Design 2000, 6: 547-67. PMID: 10788596, DOI: 10.2174/1381612003400777.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-HIV AgentsDrug DesignHIV Reverse TranscriptaseHIV-1HumansReverse Transcriptase InhibitorsConceptsCatalytic cycleIntrinsic binding affinityHIV-1 reverse transcriptaseCatalytic complexChemical catalysisBinding affinityCatalysisMolecular forcesReverse transcriptase inhibitorsAllosteric siteClasses of approved drugsNon-nucleoside reverse transcriptase inhibitorsTranscriptase inhibitorsNucleoside reverse transcriptase inhibitorsSite of inhibitionEnzyme inhibitionReverse transcriptaseAlternative substratesEnzymeMechanism of Inhibition of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase by d4TTP: an Equivalent Incorporation Efficiency Relative to the Natural Substrate dTTP
Vaccaro J, Parnell K, Terezakis S, Anderson K. Mechanism of Inhibition of the Human Immunodeficiency Virus Type 1 Reverse Transcriptase by d4TTP: an Equivalent Incorporation Efficiency Relative to the Natural Substrate dTTP. Antimicrobial Agents And Chemotherapy 2000, 44: 217-221. PMID: 10602755, PMCID: PMC89660, DOI: 10.1128/aac.44.1.217-221.2000.Peer-Reviewed Original ResearchConceptsHIV-1HIV-1 RTHuman immunodeficiency virus type 1Immunodeficiency virus type 1Target human immunodeficiency virus type 1Inhibition of HIV-1 RTNatural substrateVirus type 1Pre-steady-state kinetic analysisNucleoside analogue inhibitorsDNA synthesisRNA-dependent DNA synthesisAIDS patientsPrimer-template complexHuman immunodeficiency virus type 1 reverse transcriptaseNucleoside triphosphate analoguesType 1Mechanism of inhibitionD4TTPIncorporation efficiencyDTTPDNATriphosphate analoguesAnalogue inhibitorsInhibition
1998
Mechanistic Studies Comparing the Incorporation of (+) and (−) Isomers of 3TCTP by HIV-1 Reverse Transcriptase †
Feng J, Anderson K. Mechanistic Studies Comparing the Incorporation of (+) and (−) Isomers of 3TCTP by HIV-1 Reverse Transcriptase †. Biochemistry 1998, 38: 55-63. PMID: 9890882, DOI: 10.1021/bi982340r.Peer-Reviewed Original Research
1997
Pre-Steady-State Kinetic Characterization of Wild Type and 3‘-Azido-3‘-deoxythymidine (AZT) Resistant Human Immunodeficiency Virus Type 1 Reverse Transcriptase: Implication of RNA Directed DNA Polymerization in the Mechanism of AZT Resistance †
Kerr S, Anderson K. Pre-Steady-State Kinetic Characterization of Wild Type and 3‘-Azido-3‘-deoxythymidine (AZT) Resistant Human Immunodeficiency Virus Type 1 Reverse Transcriptase: Implication of RNA Directed DNA Polymerization in the Mechanism of AZT Resistance †. Biochemistry 1997, 36: 14064-14070. PMID: 9369478, DOI: 10.1021/bi9713862.Peer-Reviewed Original Research