2005
A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design
Card GL, Blasdel L, England BP, Zhang C, Suzuki Y, Gillette S, Fong D, Ibrahim PN, Artis DR, Bollag G, Milburn MV, Kim SH, Schlessinger J, Zhang KY. A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design. Nature Biotechnology 2005, 23: 201-207. PMID: 15685167, DOI: 10.1038/nbt1059.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCrystallographyDrug Delivery SystemsDrug DesignPeptide FragmentsPeptide LibraryPhosphodiesterase InhibitorsPhosphoric Diester HydrolasesProtein BindingProtein Interaction MappingConceptsDrug designX-ray crystallographyStructural analysisChemical synthesisDetailed structural analysisScaffold derivativesPyrazole derivativesChemical substitutionPotent PDE4 inhibitorsCarboxylic estersCellular processesDrug candidatesMolecular basisNew inhibitorsCyclic nucleotide phosphodiesterasesCocrystallographyLarge familyCompoundsNucleotide phosphodiesterasesDerivativesPhosphodiesterasesCrystallographyInhibitorsEfficient methodFamily
2004
Structural Basis for the Activity of Drugs that Inhibit Phosphodiesterases
Card GL, England BP, Suzuki Y, Fong D, Powell B, Lee B, Luu C, Tabrizizad M, Gillette S, Ibrahim PN, Artis DR, Bollag G, Milburn MV, Kim SH, Schlessinger J, Zhang KY. Structural Basis for the Activity of Drugs that Inhibit Phosphodiesterases. Structure 2004, 12: 2233-2247. PMID: 15576036, DOI: 10.1016/j.str.2004.10.004.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCrystallography, X-RayPhosphodiesterase InhibitorsPhosphoric Diester HydrolasesProtein Structure, TertiaryConceptsHigh-resolution crystal structuresInvariant glutamineHydrogen bondingCatalytic domainStructural basisStructural insightsIsoform-selective inhibitorsHydrolysis of cAMPHydrophobic residuesInhibitor bindingActive siteCrystal structureCocrystal structureHydrophobic clampLarge familyDifferent inhibitorsPhosphodiesterasesVariety of diseasesSelective PDE inhibitorsInhibitorsActivity of drugsPDE inhibitorsBondingEnzymeResidues