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 inhibitorsHIVPatientsNevirapineEfavirenz
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
Crystallographic and Receptor Binding Characterization of Plasmodium falciparum Macrophage Migration Inhibitory Factor Complexed to Two Potent Inhibitors
Pantouris G, Rajasekaran D, Garcia AB, Ruiz VG, Leng L, Jorgensen WL, Bucala R, Lolis EJ. Crystallographic and Receptor Binding Characterization of Plasmodium falciparum Macrophage Migration Inhibitory Factor Complexed to Two Potent Inhibitors. Journal Of Medicinal Chemistry 2014, 57: 8652-8656. PMID: 25268646, PMCID: PMC4207548, DOI: 10.1021/jm501168q.Peer-Reviewed Original ResearchStructural studies provide clues for analog design of specific inhibitors of Cryptosporidium hominis thymidylate synthase–dihydrofolate reductase
Kumar VP, Cisneros JA, Frey KM, Castellanos-Gonzalez A, Wang Y, Gangjee A, White AC, Jorgensen WL, Anderson KS. Structural studies provide clues for analog design of specific inhibitors of Cryptosporidium hominis thymidylate synthase–dihydrofolate reductase. Bioorganic & Medicinal Chemistry Letters 2014, 24: 4158-4161. PMID: 25127103, PMCID: PMC4427026, DOI: 10.1016/j.bmcl.2014.07.049.Peer-Reviewed Original ResearchConceptsCompound 1Crystal structureActive siteCryptosporidium hominisSpecific inhibitorHydrogen-bonding interactionsDHFR active siteFolate biosynthesis pathwaySynthase-dihydrofolate reductaseTS active siteLead compound 1Van der WaalsDihydrofolate reductase enzymeBiosynthesis pathwayBond interactionsEssential enzymeHuman enzymeInhibitor methotrexateNovel seriesDer WaalsDrug targetsProtein residuesSubstrate analoguesStructural studiesReductase enzyme
2013
Virtual screening reveals allosteric inhibitors of the Toxoplasma gondii thymidylate synthase–dihydrofolate reductase
Sharma H, Landau MJ, Sullivan TJ, Kumar VP, Dahlgren MK, Jorgensen WL, Anderson KS. Virtual screening reveals allosteric inhibitors of the Toxoplasma gondii thymidylate synthase–dihydrofolate reductase. Bioorganic & Medicinal Chemistry Letters 2013, 24: 1232-1235. PMID: 24440298, PMCID: PMC3946055, DOI: 10.1016/j.bmcl.2013.12.039.Peer-Reviewed Original ResearchConceptsThymidylate synthase-dihydrofolate reductaseSynthase-dihydrofolate reductaseVirtual screeningSmall drug-like moleculesAllosteric inhibitorsDrug-like moleculesSpecies-specific inhibitorsNovel allosteric inhibitorsSuitable drug targetsTS domainParasite Toxoplasma gondiiAllosteric inhibitionDrug targetsTS activityReductaseToxoplasma gondiiInhibitorsCompoundsMoleculesEnzymeScreeningFoundations of Biomolecular Modeling
Jorgensen WL. Foundations of Biomolecular Modeling. Cell 2013, 155: 1199-1202. PMID: 24315087, PMCID: PMC3892588, DOI: 10.1016/j.cell.2013.11.023.Peer-Reviewed Original ResearchPicomolar 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 ResearchExtension into the entrance channel of HIV-1 reverse transcriptase—Crystallography and enhanced solubility
Bollini M, Frey KM, Cisneros JA, Spasov KA, Das K, Bauman JD, Arnold E, Anderson KS, Jorgensen WL. Extension into the entrance channel of HIV-1 reverse transcriptase—Crystallography and enhanced solubility. Bioorganic & Medicinal Chemistry Letters 2013, 23: 5209-5212. PMID: 23899617, PMCID: PMC3761378, DOI: 10.1016/j.bmcl.2013.06.093.Peer-Reviewed Original ResearchOptimization of diarylazines as anti-HIV agents with dramatically enhanced solubility
Bollini M, Cisneros JA, Spasov KA, Anderson KS, Jorgensen WL. Optimization of diarylazines as anti-HIV agents with dramatically enhanced solubility. Bioorganic & Medicinal Chemistry Letters 2013, 23: 5213-5216. PMID: 23937980, PMCID: PMC3759246, DOI: 10.1016/j.bmcl.2013.06.091.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 ResearchCrystal 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 ResearchVirtual Screening and Optimization Yield Low-Nanomolar Inhibitors of the Tautomerase Activity of Plasmodium falciparum Macrophage Migration Inhibitory Factor
Dahlgren MK, Garcia AB, Hare AA, Tirado-Rives J, Leng L, Bucala R, Jorgensen WL. Virtual Screening and Optimization Yield Low-Nanomolar Inhibitors of the Tautomerase Activity of Plasmodium falciparum Macrophage Migration Inhibitory Factor. Journal Of Medicinal Chemistry 2012, 55: 10148-10159. PMID: 23067344, PMCID: PMC3509768, DOI: 10.1021/jm301269s.Peer-Reviewed Original ResearchConceptsImmune responsePlasmodium falciparum macrophage migration inhibitory factorInhibitory factorMacrophage migration inhibitory factorTautomerase activityMacrophage migratory inhibitory factorMigration inhibitory factorHost immune responseMalaria infectionSmall molecule inhibitorsCytokine activityHuman MIFHuman cytokinesPlasmodium falciparum orthologuePfMIFInhibitorsLow nanomolar inhibitorsScreeningVirtual screeningCytokinesEnzymatic siteActivityInfectionSmall‐Molecule Inhibitors of the Interaction between the E3 Ligase VHL and HIF1α
Buckley DL, Gustafson JL, Van Molle I, Roth AG, Tae HS, Gareiss PC, Jorgensen WL, Ciulli A, Crews CM. Small‐Molecule Inhibitors of the Interaction between the E3 Ligase VHL and HIF1α. Angewandte Chemie International Edition 2012, 51: 11463-11467. PMID: 23065727, PMCID: PMC3519281, DOI: 10.1002/anie.201206231.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 ResearchEfficient Discovery of Potent Anti-HIV Agents Targeting the Tyr181Cys Variant of HIV Reverse Transcriptase
Jorgensen WL, Bollini M, Thakur VV, Domaoal RA, Spasov KA, Anderson KS. Efficient Discovery of Potent Anti-HIV Agents Targeting the Tyr181Cys Variant of HIV Reverse Transcriptase. Journal Of The American Chemical Society 2011, 133: 15686-15696. PMID: 21853995, PMCID: PMC3183387, DOI: 10.1021/ja2058583.Peer-Reviewed Original ResearchConceptsHuman immunodeficiency virusWild-type HIV-1HIV-1Potent Anti-HIV AgentsInfected human T cellsNon-nucleoside reverseAnti-HIV AgentsHuman T cellsHIV reverse transcriptaseImmunodeficiency virusT cellsHIV RTViral strainsHIV agentsPresent reportReverse transcriptaseNM potencyCritical contributorPotential benefits
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 ResearchDiscovery of Novel Fibroblast Growth Factor Receptor 1 Kinase Inhibitors by Structure-Based Virtual Screening
Ravindranathan KP, Mandiyan V, Ekkati AR, Bae JH, Schlessinger J, Jorgensen WL. Discovery of Novel Fibroblast Growth Factor Receptor 1 Kinase Inhibitors by Structure-Based Virtual Screening. Journal Of Medicinal Chemistry 2010, 53: 1662-1672. PMID: 20121196, PMCID: PMC2842983, DOI: 10.1021/jm901386e.Peer-Reviewed Original ResearchConceptsFibroblast growth factorCo-crystal structureKinase structureFGFR1 kinaseSearch of inhibitorsEmbryonic developmentProtein structureAlternative conformationsCell proliferationStructural motifsKinase inhibitorsGrowth factorNew structural motifDiverse compoundsVirtual screeningFGFR1InhibitorsDockingWound healingThienopyrimidinone derivativesImportant roleConformationKinaseProteinMotif
2009
In Silico Improvement of β3-Peptide Inhibitors of p53•hDM2 and p53•hDMX
Michel J, Harker EA, Tirado-Rives J, Jorgensen WL, Schepartz A. In Silico Improvement of β3-Peptide Inhibitors of p53•hDM2 and p53•hDMX. Journal Of The American Chemical Society 2009, 131: 6356-6357. PMID: 19415930, PMCID: PMC2754742, DOI: 10.1021/ja901478e.Peer-Reviewed Original Research