2017
JAK2 JH2 Fluorescence Polarization Assay and Crystal Structures for Complexes with Three Small Molecules
Newton AS, Deiana L, Puleo DE, Cisneros J, Cutrona KJ, Schlessinger J, Jorgensen WL. JAK2 JH2 Fluorescence Polarization Assay and Crystal Structures for Complexes with Three Small Molecules. ACS Medicinal Chemistry Letters 2017, 8: 614-617. PMID: 28626520, PMCID: PMC5467202, DOI: 10.1021/acsmedchemlett.7b00154.Peer-Reviewed Original Research
2014
Structural 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 enzymeA 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 ResearchConceptsSolvent 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 ResearchConceptsHalogen-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