2017
Covalent inhibitors for eradication of drug-resistant HIV-1 reverse transcriptase: From design to protein crystallography
Chan AH, Lee WG, Spasov KA, Cisneros JA, Kudalkar SN, Petrova ZO, Buckingham AB, Anderson KS, Jorgensen WL. Covalent inhibitors for eradication of drug-resistant HIV-1 reverse transcriptase: From design to protein crystallography. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 9725-9730. PMID: 28827354, PMCID: PMC5594698, DOI: 10.1073/pnas.1711463114.Peer-Reviewed Original ResearchConceptsHIV-1 reverse transcriptaseNonnucleoside RT inhibitorsDrug-resistant HIV-1 reverse transcriptaseReverse transcriptaseHIV-1 infectionTreatment of HIVT cell assaysDevelopment of resistanceRT inhibitorsAntiviral activityDrug efavirenzClass drugsInhibitorsViral polymeraseDrugsEnzyme inhibition kineticsResistant mutantsConclusive evidenceTranscriptasePoint mutationsCovalent inhibitorsHIVPatientsNevirapineEfavirenzStructural and Preclinical Studies of Computationally-Designed Non-nucleoside Reverse Transcriptase Inhibitors for Treating HIV infection
Kudalkar SN, Beloor J, Chan AH, Lee WG, Jorgensen WL, Kumar P, Anderson KS. Structural and Preclinical Studies of Computationally-Designed Non-nucleoside Reverse Transcriptase Inhibitors for Treating HIV infection. Molecular Pharmacology 2017, 91: mol.116.107755. PMID: 28167742, PMCID: PMC5363707, DOI: 10.1124/mol.116.107755.Peer-Reviewed Original ResearchConceptsNon-nucleoside reverse transcriptase inhibitorBALB/c miceReverse transcriptase inhibitorHIV infectionC miceTranscriptase inhibitorAntiviral activityCompound INew non-nucleoside reverse transcriptase inhibitorHIV-1 non-nucleoside reverse transcriptase inhibitorDetectable acute toxicityTreating HIV InfectionSingle intraperitoneal doseAnti-HIV-1 potencyMT-2 cellsDrug-resistant variantsCompound IISerum residence timeAnti-viral potencyHIV-1 RTClinical benefitClinical efficacyIntraperitoneal doseWild-type HIV-1 RTPlasma clearance
2016
Computer-aided discovery of anti-HIV agents
Jorgensen WL. Computer-aided discovery of anti-HIV agents. Bioorganic & Medicinal Chemistry 2016, 24: 4768-4778. PMID: 27485603, PMCID: PMC5114837, DOI: 10.1016/j.bmc.2016.07.039.Peer-Reviewed Original Research
2015
Discovery and crystallography of bicyclic arylaminoazines as potent inhibitors of HIV-1 reverse transcriptase
Lee WG, Frey KM, Gallardo-Macias R, Spasov KA, Chan AH, Anderson KS, Jorgensen WL. Discovery and crystallography of bicyclic arylaminoazines as potent inhibitors of HIV-1 reverse transcriptase. Bioorganic & Medicinal Chemistry Letters 2015, 25: 4824-4827. PMID: 26166629, PMCID: PMC4607639, DOI: 10.1016/j.bmcl.2015.06.074.Peer-Reviewed Original ResearchStructure-Based Evaluation of Non-nucleoside Inhibitors with Improved Potency and Solubility That Target HIV Reverse Transcriptase Variants
Frey KM, Puleo DE, Spasov KA, Bollini M, Jorgensen WL, Anderson KS. Structure-Based Evaluation of Non-nucleoside Inhibitors with Improved Potency and Solubility That Target HIV Reverse Transcriptase Variants. Journal Of Medicinal Chemistry 2015, 58: 2737-2745. PMID: 25700160, PMCID: PMC4378236, DOI: 10.1021/jm501908a.Peer-Reviewed Original Research
2014
A mechanistic and structural investigation of modified derivatives of the diaryltriazine class of NNRTIs targeting HIV-1 reverse transcriptase
Mislak AC, Frey KM, Bollini M, Jorgensen WL, Anderson KS. A mechanistic and structural investigation of modified derivatives of the diaryltriazine class of NNRTIs targeting HIV-1 reverse transcriptase. Biochimica Et Biophysica Acta 2014, 1840: 2203-2211. PMID: 24726448, PMCID: PMC4061246, DOI: 10.1016/j.bbagen.2014.04.001.Peer-Reviewed Original ResearchMeSH KeywordsCrystallography, X-RayDrug DesignHIV InfectionsHIV Reverse TranscriptaseHIV-1HumansKineticsMechanical PhenomenaMorpholinesProtein ConformationReverse Transcriptase InhibitorsTriazinesConceptsSolvent interfaceStructure-based drug designCatalytic site geometryPhysiochemical propertiesFuture inhibitor developmentTransient-state kinetic analysisImproved pharmacological propertiesImproved pharmacological profileAzine ringPolymerization stepMorpholine derivativesCrystal structureLow nanomolar potencyDrug designSubstituentsStructural investigationsSite geometryImproved physiochemical propertiesNew inhibitorsNanomolar potencyLow nanomolar antiviral activityDerivativesStructural basisStructural analysisNon-nucleoside inhibitorsStructure‐Based Evaluation of C5 Derivatives in the Catechol Diether Series Targeting HIV‐1 Reverse Transcriptase
Frey KM, Gray WT, Spasov KA, Bollini M, Gallardo‐Macias R, Jorgensen WL, Anderson KS. Structure‐Based Evaluation of C5 Derivatives in the Catechol Diether Series Targeting HIV‐1 Reverse Transcriptase. Chemical Biology & Drug Design 2014, 83: 541-549. PMID: 24289305, PMCID: PMC3999282, DOI: 10.1111/cbdd.12266.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCatecholsDrug DesignHIV Reverse TranscriptaseHIV-1Hydrogen BondingMolecular Dynamics SimulationProtein Structure, TertiaryReverse Transcriptase InhibitorsStructure-Activity RelationshipUracilConceptsHalogen-bonding interactionsCrystal structureHydrogen bondsAdditional hydrogen bond interactionC5 substitutionVan der Waals interactionsHydrogen-bonding interactionsAdditional crystal structuresDer Waals interactionsMore hydrogen bondsEffect of substituentsWaals interactionsClass of inhibitorsBackbone carbonylC5 substituentC5 positionComputational studyComparative structural analysisCatechol diethersStructure-based evaluationDerivativesSubstituentsHIV-1 reverse transcriptasePicomolar potencyBonds
2013
Picomolar Inhibitors of HIV Reverse Transcriptase Featuring Bicyclic Replacement of a Cyanovinylphenyl Group
Lee WG, Gallardo-Macias R, Frey KM, Spasov KA, Bollini M, Anderson KS, Jorgensen WL. Picomolar Inhibitors of HIV Reverse Transcriptase Featuring Bicyclic Replacement of a Cyanovinylphenyl Group. Journal Of The American Chemical Society 2013, 135: 16705-16713. PMID: 24151856, PMCID: PMC3877923, DOI: 10.1021/ja408917n.Peer-Reviewed Original Research
2012
Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency
Bollini M, Gallardo-Macias R, Spasov KA, Tirado-Rives J, Anderson KS, Jorgensen WL. Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency. Bioorganic & Medicinal Chemistry Letters 2012, 23: 1110-1113. PMID: 23298809, PMCID: PMC3561933, DOI: 10.1016/j.bmcl.2012.11.115.Peer-Reviewed Original ResearchMeSH KeywordsAnti-HIV AgentsDrug DesignHIV Reverse TranscriptaseHIV-1HumansModels, MolecularReverse Transcriptase InhibitorsStructure-Activity RelationshipCrystal Structures of HIV‑1 Reverse Transcriptase with Picomolar Inhibitors Reveal Key Interactions for Drug Design
Frey KM, Bollini M, Mislak AC, Cisneros J, Gallardo-Macias R, Jorgensen WL, Anderson KS. Crystal Structures of HIV‑1 Reverse Transcriptase with Picomolar Inhibitors Reveal Key Interactions for Drug Design. Journal Of The American Chemical Society 2012, 134: 19501-19503. PMID: 23163887, PMCID: PMC3518392, DOI: 10.1021/ja3092642.Peer-Reviewed Original Research
2011
Computationally-Guided Optimization of a Docking Hit to Yield Catechol Diethers as Potent Anti-HIV Agents
Bollini M, Domaoal RA, Thakur VV, Gallardo-Macias R, Spasov KA, Anderson KS, Jorgensen WL. Computationally-Guided Optimization of a Docking Hit to Yield Catechol Diethers as Potent Anti-HIV Agents. Journal Of Medicinal Chemistry 2011, 54: 8582-8591. PMID: 22081993, PMCID: PMC3258498, DOI: 10.1021/jm201134m.Peer-Reviewed Original Research
2010
Eastern extension of azoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase; cyano group alternatives
Leung CS, Zeevaart JG, Domaoal RA, Bollini M, Thakur VV, Spasov KA, Anderson KS, Jorgensen WL. Eastern extension of azoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase; cyano group alternatives. Bioorganic & Medicinal Chemistry Letters 2010, 20: 2485-2488. PMID: 20304641, PMCID: PMC2880392, DOI: 10.1016/j.bmcl.2010.03.006.Peer-Reviewed Original Research
2009
Discovery of Wild-Type and Y181C Mutant Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors Using Virtual Screening with Multiple Protein Structures
Nichols SE, Domaoal RA, Thakur VV, Tirado-Rives J, Anderson KS, Jorgensen WL. Discovery of Wild-Type and Y181C Mutant Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors Using Virtual Screening with Multiple Protein Structures. Journal Of Chemical Information And Modeling 2009, 49: 1272-1279. PMID: 19374380, PMCID: PMC2817966, DOI: 10.1021/ci900068k.Peer-Reviewed Original ResearchMeSH KeywordsDrug DesignDrug Evaluation, PreclinicalModels, MolecularReverse Transcriptase InhibitorsConceptsNon-nucleoside HIV-1 reverse transcriptase inhibitorReverse transcriptase inhibitorHIV-1 reverse transcriptaseHIV-1 Reverse Transcriptase InhibitorsTranscriptase inhibitorHIV-1RT mutationsNon-nucleoside inhibitorsAntiviral activityHIV agentsWild-type virusResistance profilesWT virusReverse transcriptaseInhibitorsScreeningVirtual screening
2007
From Docking False-Positive to Active Anti-HIV Agent
Barreiro G, Kim JT, Guimarães CR, Bailey CM, Domaoal RA, Wang L, Anderson KS, Jorgensen WL. From Docking False-Positive to Active Anti-HIV Agent. Journal Of Medicinal Chemistry 2007, 50: 5324-5329. PMID: 17918923, PMCID: PMC2575345, DOI: 10.1021/jm070683u.Peer-Reviewed Original Research
2006
FEP-Guided Selection of Bicyclic Heterocycles in Lead Optimization for Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase
Kim JT, Hamilton AD, Bailey CM, Domoal R, Wang L, Anderson KS, Jorgensen WL. FEP-Guided Selection of Bicyclic Heterocycles in Lead Optimization for Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase. Journal Of The American Chemical Society 2006, 128: 15372-15373. PMID: 17131993, DOI: 10.1021/ja066472g.Peer-Reviewed Original Research
2005
Optimization of diarylamines as non-nucleoside inhibitors of HIV-1 reverse transcriptase
Ruiz-Caro J, Basavapathruni A, Kim JT, Bailey CM, Wang L, Anderson KS, Hamilton AD, Jorgensen WL. Optimization of diarylamines as non-nucleoside inhibitors of HIV-1 reverse transcriptase. Bioorganic & Medicinal Chemistry Letters 2005, 16: 668-671. PMID: 16298131, DOI: 10.1016/j.bmcl.2005.10.037.Peer-Reviewed Original ResearchComputer-aided design of non-nucleoside inhibitors of HIV-1 reverse transcriptase
Jorgensen WL, Ruiz-Caro J, Tirado-Rives J, Basavapathruni A, Anderson KS, Hamilton AD. Computer-aided design of non-nucleoside inhibitors of HIV-1 reverse transcriptase. Bioorganic & Medicinal Chemistry Letters 2005, 16: 663-667. PMID: 16263277, DOI: 10.1016/j.bmcl.2005.10.038.Peer-Reviewed Original Research