grant
Studies of lipoamide dehydrogenase tight binding inhibition in tuberculous and non-tuberculous mycobacteria
Organization WEILL MEDICAL COLL OF CORNELL UNIVLocation NEW YORK, UNITED STATESPosted 22 Nov 2023Deadline 31 Oct 2028
NIHUS FederalResearch GrantFY20261,2-dithiolane-3-valeramide6,8-thioctic amideAcyltransferaseAffinityAnti-Bacterial AgentsAntibiotic AgentsAntibiotic DrugsAntibioticsAntioxidantsAntitubercular DrugsAssayBacteriaBacterial InfectionsBindingBinding SitesBioassayBiological AssayBiologyBiophysicsBone MarrowBone Marrow Reticuloendothelial SystemCOVID-19 pandemic affectedCOVID-19 pandemic consequenceCOVID-19 pandemic effectsCOVID-19 pandemic impactCOVID-19 pandemic impactedCause of DeathCell BodyCellsCessation of lifeChemicalsClinicalCollaborationsCombining SiteComplexCryo-electron MicroscopyCryoelectron MicroscopyData CorrelationsDeathDedicationsDehydrogenasesDevelopmentDihydrolipoyl DehydrogenaseDiseaseDisease ManagementDisorderDisorder ManagementDoseDrug resistanceDrugsEC 2.3Electron CryomicroscopyEnzyme AntagonistEnzyme GeneEnzyme InhibitorEnzyme Inhibitor AgentEnzyme Inhibitor DrugsEnzyme KineticsEnzymesExclusion ChromatographyFDA approvedGel ChromatographyGel FiltrationGel Filtration ChromatographyGel Permeation ChromatographyGeneralized GrowthGenus MycobacteriumGrowthHemi-MyeloperoxidaseImmunocompetentImmunocompromisedImmunocompromised HostImmunocompromised PatientImmunosuppressed HostIn VitroIndividualInfectionInstitutionIntermediary MetabolismKeto AcidsKnowledgeLibrariesLipoamide DehydrogenaseLipoic Acid DehydrogenaseLipoyl DehydrogenaseLong-term infectionM abscessusM aviumM tbM tuberculosisM tuberculosis infectionM. abscessusM. aviumM. tbM. tb infectionM. tuberculosisM. tuberculosis complexM. tuberculosis infectionM.tb complexM.tb infectionM.tuberculosis infectionMTB infectionMacromolecular StructureMacrophageMeasuresMedicationMetabolicMetabolic ProcessesMetabolismMiceMice MammalsMiscellaneous AntibioticMolecular InteractionMolecular StructureMtb complexMultienzyme ComplexesMurineMusMycobacteriumMycobacterium abscessusMycobacterium aviumMycobacterium tuberculosisMycobacterium tuberculosis (MTB) infectionMycobacterium tuberculosis complexMycobacterium tuberculosis infectionMycobacteroides abscessusMyeloperoxidaseMφNAD DiaphoraseNADH DiaphoraseNTM infectionNitroimidazolesOrthologOrthologous GeneOxidoreductaseOxidoreductase GenePathogenicityPeroxidasesPharmaceutical PreparationsPost-Translational Modification Protein/Amino Acid BiochemistryPost-Translational ModificationsPost-Translational Protein ModificationPost-Translational Protein ProcessingPosttranslational ModificationsPosttranslational Protein ProcessingProtein ModificationProteinsPyruvate Dehydrogenase ComplexReactive SiteRecombinantsReductasesRegimenResearch InstituteResistanceServicesStructureStructure-Activity RelationshipSulfonamidesTB drugsTB infectionTestingTherapeuticTherapeutic IndexTimeTissue GrowthToxic effectToxicitiesTreatment ProtocolsTreatment RegimenTreatment ScheduleTuberculosisacute infectionalpha-lipoic amideanaloganti-TB drugsanti-bacterialanti-tuberculosis drugsaxenic culturebacteria infectionbacterial diseasebiophysical foundationbiophysical principlesbiophysical scienceschemical structure functionchronic infectioncoronavirus disease 2019 pandemic consequencecoronavirus disease 2019 pandemic impactcryo-EMcryoEMcryogenic electron microscopydata modelingdesigndesigningdevelopmentaldiaphorasedihydrolipoamide dehydrogenasedisseminated TBdisseminated tuberculosisdrug resistantdrug/agenteffects following the COVID-19 pandemicenzyme complexglobal health emergencyhigh definitionhigh-resolutionimmune competentimmunosuppressed patientimpact of the SARS-CoV-2 pandemicimprovedin vivoinfection due to Mycobacterium tuberculosisinhibitorketoacidketoglutarate dehydrogenaselead candidatelipamidelipoamidemetabolism measurementmetabolomicsmetabonomicsmodel of datamodel the datamodeling of the datamortalitymouse modelmtbmurine modelmycobacterialnon-compliancenon-compliantnon-tuberculosis mycobacterianon-tuberculosis mycobacterialnon-tuberculous mycobacterianon-tuberculous mycobacterialnon-tuberculous mycobacterial infectionnoncompliancenoncompliantnontuberculosis mycobacterialnontuberculous mycobacterianontuberculous mycobacterialnovelontogenypathogenperoxynitrite reductasepersistent infectionprotein complexpyruvate dehydrogenaseresidenceresidential buildingresidential siteresistance to Drugresistantresistant to Drugscaffoldscaffoldingstructure function relationshiptooltuberculosis drugstuberculosis infectiontuberculous spondyloarthropathy
Description preview
SUMMARY
Tuberculosis (TB) is the leading cause of death from a single infection worldwide, with an annual death toll of
over 1.6 million lives. TB is curable and drug regimens can be above 90% effective if completed but are long and
toxic leading to noncompliance and emergence of resistance. New treatment options relying on novel and
unexplored…
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