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
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