2017
Adding a Hydrogen Bond May Not Help: Naphthyridinone vs Quinoline Inhibitors of Macrophage Migration Inhibitory Factor
Dawson TK, Dziedzic P, Robertson MJ, Cisneros J, Krimmer SG, Newton AS, Tirado-Rives J, Jorgensen WL. Adding a Hydrogen Bond May Not Help: Naphthyridinone vs Quinoline Inhibitors of Macrophage Migration Inhibitory Factor. ACS Medicinal Chemistry Letters 2017, 8: 1287-1291. PMID: 29259749, PMCID: PMC5733268, DOI: 10.1021/acsmedchemlett.7b00384.Peer-Reviewed Original ResearchHydrogen bondsFEP resultsProtein-ligand hydrogen bondsExcellent aqueous solubilityLactam carbonyl groupDFT calculationsAqueous solubilityAmmonium groupsCarbonyl groupN distancesActive siteCrystal structureBondsQuinoline inhibitorsRelated quinolinesQuinolineNaphthyridinonesModel systemSolubilityCompoundsComplexesLys32CoordinationNMCalculations
2016
Elucidating the Origin of Long Residence Time Binding for Inhibitors of the Metalloprotease Thermolysin
Cramer J, Krimmer S, Fridh V, Wulsdorf T, Karlsson R, Heine A, Klebe G. Elucidating the Origin of Long Residence Time Binding for Inhibitors of the Metalloprotease Thermolysin. ACS Chemical Biology 2016, 12: 225-233. PMID: 27959500, DOI: 10.1021/acschembio.6b00979.Peer-Reviewed Original ResearchConceptsCharge-assisted hydrogen bondsMetalloprotease thermolysinSurface plasmon resonance spectroscopyDrug discoveryHigh-resolution crystal structuresPlasmon resonance spectroscopyKinetic dataProtein-ligand interactionsStructure-kinetic relationshipsRational drug discoveryHigh conservationHydrogen bondsDissociation rate constantsStrength of interactionThermolysin inhibitorsMetalloprotease familyCrystal structureMolecular mechanismsSide chainsStrand motifResonance spectroscopyStructural motifsRate constantsRate-limiting stepLigand release