Karen Anthony
Staff Affiliate - OtherCards
About
Research
Publications
2019
Inhibition of Macrophage Migration Inhibitory Factor by a Chimera of Two Allosteric Binders
Cirillo PF, Asojo OA, Khire U, Lee Y, Mootien S, Hegan P, Sutherland AG, Peterson-Roth E, Ledizet M, Koski RA, Anthony KG. Inhibition of Macrophage Migration Inhibitory Factor by a Chimera of Two Allosteric Binders. ACS Medicinal Chemistry Letters 2019, 11: 1843-1847. PMID: 33062162, PMCID: PMC7549106, DOI: 10.1021/acsmedchemlett.9b00351.Peer-Reviewed Original ResearchMacrophage migration inhibitory factorMore drug-like compoundsDrug-like compoundsPro-inflammatory activityX-ray crystallographyRational design strategyMigration inhibitory factorChemistry leadAllosteric bindersSite-specific inhibitorsInhibitory factorAllosteric pocketStructural liabilitiesHuman macrophage migration inhibitory factorCompoundsInhibitory propertiesChimeric compoundsDesign strategyAutoimmune diseasesUnique strategyReceptor bindingCrystallographyDrug developmentSynthesisTrimer
2014
Structural and biochemical analyses of alanine racemase from the multidrug-resistant Clostridium difficile strain 630
Asojo OA, Nelson SK, Mootien S, Lee Y, Rezende WC, Hyman DA, Matsumoto MM, Reiling S, Kelleher A, Ledizet M, Koski RA, Anthony KG. Structural and biochemical analyses of alanine racemase from the multidrug-resistant Clostridium difficile strain 630. Acta Crystallographica Section D, Structural Biology 2014, 70: 1922-1933. PMID: 25004969, PMCID: PMC4089486, DOI: 10.1107/s1399004714009419.Peer-Reviewed Original Research
2013
Inhibition of mycobacterial alanine racemase activity and growth by thiadiazolidinones
Lee Y, Mootien S, Shoen C, Destefano M, Cirillo P, Asojo OA, Yeung KR, Ledizet M, Cynamon MH, Aristoff PA, Koski RA, Kaplan PA, Anthony KG. Inhibition of mycobacterial alanine racemase activity and growth by thiadiazolidinones. Biochemical Pharmacology 2013, 86: 222-230. PMID: 23680030, PMCID: PMC3700342, DOI: 10.1016/j.bcp.2013.05.004.Peer-Reviewed Original ResearchConceptsM. tuberculosisMinimal inhibitory concentrationDrug-susceptible M. tuberculosisDrug-resistant M. tuberculosisResistant strainsInhibitory concentrationTreatment of tuberculosisMultidrug-resistant strainsTreatment courseNovel antimycobacterial agentsMedicinal chemistry effortsTuberculosisFamily of compoundsAntimycobacterial agentsCausative agentChemistry effortsM. smegmatisHeterocyclic classNew antibioticsBacterial resistanceAntibioticsInhibitionNon-pathogenic speciesThiadiazolidinonesPathogenic species
2012
A Novel Allosteric Inhibitor of Macrophage Migration Inhibitory Factor (MIF)*
Bai F, Asojo OA, Cirillo P, Ciustea M, Ledizet M, Aristoff PA, Leng L, Koski RA, Powell TJ, Bucala R, Anthony KG. A Novel Allosteric Inhibitor of Macrophage Migration Inhibitory Factor (MIF)*. Journal Of Biological Chemistry 2012, 287: 30653-30663. PMID: 22782901, PMCID: PMC3436310, DOI: 10.1074/jbc.m112.385583.Peer-Reviewed Original ResearchConceptsInteraction of MIFNovel allosteric inhibitorsHydrogen bondingNoncovalent interactionsAzo compoundsChemical probesDifferent monomersSingle moleculesHydrophobic interactionsSmall moleculesProtein surfaceStructural studiesRegulatory propertiesCatalytic prolineAllosteric inhibitorsMoleculesTrimerFunctional characterizationSpecific residuesStructural basisUpstream mediatorSmall-molecule MIF inhibitorsUnique modeMonomersInhibitory factor
2011
Thiadiazolidinones: A new class of alanine racemase inhibitors with antimicrobial activity against methicillin-resistant Staphylococcus aureus
Ciustea M, Mootien S, Rosato AE, Perez O, Cirillo P, Yeung KR, Ledizet M, Cynamon MH, Aristoff PA, Koski RA, Kaplan PA, Anthony KG. Thiadiazolidinones: A new class of alanine racemase inhibitors with antimicrobial activity against methicillin-resistant Staphylococcus aureus. Biochemical Pharmacology 2011, 83: 368-377. PMID: 22146584, PMCID: PMC3478562, DOI: 10.1016/j.bcp.2011.11.021.Peer-Reviewed Original ResearchConceptsAntimicrobial activityNovel enzyme inhibitorsMedicinal chemistry effortsMammalian cell toxicityMammalian cell cytotoxicityHigh-throughput screening effortNew antibacterial agentsChemistry effortsLead developmentMethicillin-resistant Staphylococcus aureusChemical propertiesAlanine racemase inhibitorsAntibacterial activityAntibacterial agentsNew classMinimal inhibitory concentrationAlanine racemaseCell toxicityMode of actionGram-positive bacteriaScreening effortsStaphylococcus aureusMRSA-related infectionsGram-negative bacteriaInhibitory concentration
2009
Fusion Loop Peptide of the West Nile Virus Envelope Protein Is Essential for Pathogenesis and Is Recognized by a Therapeutic Cross-Reactive Human Monoclonal Antibody
Sultana H, Foellmer HG, Neelakanta G, Oliphant T, Engle M, Ledizet M, Krishnan MN, Bonafé N, Anthony KG, Marasco WA, Kaplan P, Montgomery RR, Diamond MS, Koski RA, Fikrig E. Fusion Loop Peptide of the West Nile Virus Envelope Protein Is Essential for Pathogenesis and Is Recognized by a Therapeutic Cross-Reactive Human Monoclonal Antibody. The Journal Of Immunology 2009, 183: 650-660. PMID: 19535627, PMCID: PMC3690769, DOI: 10.4049/jimmunol.0900093.Peer-Reviewed Original ResearchConceptsWest Nile virus envelope proteinWest Nile virusVirus envelope proteinDengue virusCross-reactive human monoclonal antibodiesBlood-brain barrier permeabilityEnvelope proteinWest Nile virus infectionNeutralization escape variantsNile virusWest Nile encephalitisNeutralization escape mutantsHuman monoclonal antibodyFatal neurological diseaseParental West Nile virusFusion loopEscape variantsInflammatory responseBarrier permeabilityLethal encephalitisMAb11Virus infectionHuman mAbsEscape mutantsNeurological diseasesCrystal Structure of Dengue Virus Type 1 Envelope Protein in the Postfusion Conformation and Its Implications for Membrane Fusion
Nayak V, Dessau M, Kucera K, Anthony K, Ledizet M, Modis Y. Crystal Structure of Dengue Virus Type 1 Envelope Protein in the Postfusion Conformation and Its Implications for Membrane Fusion. Journal Of Virology 2009, 83: 4338-4344. PMID: 19244332, PMCID: PMC2668458, DOI: 10.1128/jvi.02574-08.Peer-Reviewed Original ResearchConceptsConformational changesPostfusion conformationFusogenic conformational changesLipid membranesEnvelope proteinViral lipid membraneTrimer contactsEndosomal membranesMembrane fusionPolar residuesDomain IDistinct conformationsViral genomePostfusion structureProteinFusion loopTight clusterCrystal structureResiduesMembraneConformationGenomeSe trimersEndosomesVirus type 1Effective siRNA targeting of the 3′ untranslated region of the West Nile virus genome
Anthony KG, Bai F, Krishnan MN, Fikrig E, Koski RA. Effective siRNA targeting of the 3′ untranslated region of the West Nile virus genome. Antiviral Research 2009, 82: 166-168. PMID: 19135091, DOI: 10.1016/j.antiviral.2008.12.007.Peer-Reviewed Original ResearchConceptsWest Nile virusSiRNA targetsSpecific antiviral therapyRelated dengue virusAntiviral therapyWNV pathogenesisShort hairpin RNA sequencesDengue virusWNV replicationTherapeutic potentialViral replicationRNA interferenceAntiviral therapeuticsSiRNA targetingPotential antiviral therapeuticsVero cellsNile virusSequence-specific inhibitorsHuman pathogensUntranslated regionVirusVirus genomeWest Nile virus genomeTargetPathogenesis
2008
A recombinant West Nile virus envelope protein vaccine candidate produced in Spodoptera frugiperda expresSF+ cells
Bonafé N, Rininger JA, Chubet RG, Foellmer HG, Fader S, Anderson JF, Bushmich SL, Anthony K, Ledizet M, Fikrig E, Koski RA, Kaplan P. A recombinant West Nile virus envelope protein vaccine candidate produced in Spodoptera frugiperda expresSF+ cells. Vaccine 2008, 27: 213-222. PMID: 18996430, PMCID: PMC2651515, DOI: 10.1016/j.vaccine.2008.10.046.Peer-Reviewed Original ResearchConceptsVaccine candidatesClinical adverse effectsProtein vaccine candidateRecombinant vaccine candidateWNV vaccineAntibody titersHumoral immunityProtective efficacySafe vaccineWNV infectionChallenge modelVaccine antigensAnimal modelsViral protectionHigh dosesProtein antigensAdverse effectsImmunogenicitySerum-free cultureAntigenCell linesNaïve foalsVaccineAluminum hydroxideInfection
2007
Antibodies Targeting Linear Determinants of the Envelope Protein Protect Mice against West Nile Virus
Ledizet M, Kar K, Foellmer HG, Bonafé N, Anthony KG, Gould LH, Bushmich SL, Fikrig E, Koski RA. Antibodies Targeting Linear Determinants of the Envelope Protein Protect Mice against West Nile Virus. Journal Of Infectious Diseases 2007, 196: 1741-1748. PMID: 18190253, DOI: 10.1086/523654.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodies, ViralAntibody AffinityChlorocebus aethiopsDrosophilaEpitopesFemaleFluorescent Antibody TechniqueHorsesImmunization, PassiveImmunoglobulinsMiceMice, Inbred C3HMolecular Sequence DataPeptide FragmentsVero CellsViral Envelope ProteinsWest Nile FeverWest Nile virusConceptsE proteinMultiple flavivirus infectionsVirus-neutralizing antibodiesE protein epitopesFlavivirus envelope proteinProtect miceWest Nile virusFlavivirus infectionLethal challengeProtective antibodiesWest Nile virus E proteinProtective epitopesVirus E proteinRelated flavivirusesImmunoglobulinAntibodiesNile virusLinear determinantsEpitopesEnvelope proteinProtein epitopesMiceHost cell membraneWNVPeptides