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
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 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 inhibitors