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 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 gondiiInhibitorsCompoundsMoleculesEnzymeScreeningExtension 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 Research
2012
Small‐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
2008
Novel non-active site inhibitor of Cryptosporidium hominis TS-DHFR identified by a virtual screen
Martucci WE, Udier-Blagovic M, Atreya C, Babatunde O, Vargo MA, Jorgensen WL, Anderson KS. Novel non-active site inhibitor of Cryptosporidium hominis TS-DHFR identified by a virtual screen. Bioorganic & Medicinal Chemistry Letters 2008, 19: 418-423. PMID: 19059777, PMCID: PMC2651159, DOI: 10.1016/j.bmcl.2008.11.054.Peer-Reviewed Original ResearchConceptsThymidylate synthase-dihydrofolate reductaseHuman enzymeNovel allosteric pocketSite inhibitorsSynthase-dihydrofolate reductaseFlavin mononucleotideActive site inhibitorsVirtual screenLinker regionAllosteric pocketInhibitor targetingSpecies specificitySite pocketDrug targetsCryptosporidium hominisNovel inhibitorsEnzymeMicromolar potencySelective inhibitorNoncompetitive inhibitorInhibitorsLead compoundsScreenPocketReductase