2025
Pantothenate kinase is an effective target for antifungal therapy
Regan J, DeJarnette C, Reitler P, Gihaz S, Srivastava A, Ge W, Tucker K, Peters T, Meibohm B, Ben Mamoun C, Fortwendel J, Hevener K, Palmer G. Pantothenate kinase is an effective target for antifungal therapy. Cell Chemical Biology 2025, 32: 710-721.e6. PMID: 40378822, DOI: 10.1016/j.chembiol.2025.04.007.Peer-Reviewed Original ResearchConceptsPantothenate kinasePathogenic yeast Candida albicansDisseminated C. albicans infectionYeast Candida albicansIn vivo antifungal efficacyChemical-genetic approachBroad-spectrum antifungalAntifungal therapeuticsCoA productionCandida albicansMammalian hostsAntifungal therapyCoenzyme ASmall molecule inhibitorsAntifungal efficacyPanKEssential cofactorChemical probesMolecule inhibitorsKinaseLiving organismsPantothenateMouse modelEffective targetVirulence
2023
Activity‐based Tools for Interrogating Host Biology During Infection
Ramanathan R, Hatzios S. Activity‐based Tools for Interrogating Host Biology During Infection. Israel Journal Of Chemistry 2023, 63 PMID: 37744997, PMCID: PMC10512441, DOI: 10.1002/ijch.202200095.Peer-Reviewed Original ResearchActivity-based protein profilingPost-translational modificationsHost post-translational modificationsHost-microbe interactionsHost biologyCells senseCell signalingMicrobial mechanismsEnzyme functionProtein profilingProtein structureSide-chain reactivityChemical probesInfected cellsHost-directed therapiesPotential targetRapid modulationHost responseSignalingBiologyInfectionEnzymeProfilingPathwayPathogens
2021
Pharmacological inhibition of PI5P4Kα/β disrupts cell energy metabolism and selectively kills p53-null tumor cells
Chen S, Tjin C, Gao X, Xue Y, Jiao H, Zhang R, Wu M, He Z, Ellman J, Ha Y. Pharmacological inhibition of PI5P4Kα/β disrupts cell energy metabolism and selectively kills p53-null tumor cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2021, 118: e2002486118. PMID: 34001596, PMCID: PMC8166193, DOI: 10.1073/pnas.2002486118.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein Kinase KinasesAnimalsEnergy MetabolismHumansInsulinInsulin Receptor Substrate ProteinsMechanistic Target of Rapamycin Complex 1MiceMuscle Fibers, SkeletalNeoplasmsPhosphorylationPhosphotransferases (Alcohol Group Acceptor)Ribosomal Protein S6 Kinases, 70-kDaSignal TransductionSmall Molecule LibrariesTumor Suppressor Protein p53ConceptsP53-null tumor cellsMost human cancer cellsCell energy homeostasisCell energy metabolismTumor suppressor genePI5P4KHuman cancer cellsGenetic experimentsDifferentiated myotubesAMPK activationStructural basisKinase activityEnergy stressMetabolic regulationSuppressor geneFunction mutationsLate-onset tumorsSubstrate loopP53 tumor suppressor geneChemical probesPI3KCell typesExquisite specificityEnergy metabolismTumor cells
2018
Carbodiimide reagents for the chemical probing of RNA structure in cells
Wang PY, Sexton AN, Culligan WJ, Simon MD. Carbodiimide reagents for the chemical probing of RNA structure in cells. RNA 2018, 25: 135-146. PMID: 30389828, PMCID: PMC6298570, DOI: 10.1261/rna.067561.118.Peer-Reviewed Original ResearchConceptsConformation of RNAU nucleotidesIntact cellsChemical probesDimethyl sulfateNucleotides of RNASingle-stranded nucleotidesXist lncRNACellular contextNoncoding RNAsRNA elementsSHAPE reagentsAccessible nucleotidesRNA conformationRNA structureBiological contextChemical probingWatson-Crick faceCellular environmentFunctional roleCarbodiimide reagentRNA nucleotidesRNANucleotidesStructured regionsActivity-Based Protein Profiling at the Host–Pathogen Interface
Kovalyova Y, Hatzios SK. Activity-Based Protein Profiling at the Host–Pathogen Interface. Current Topics In Microbiology And Immunology 2018, 420: 73-91. PMID: 30203396, DOI: 10.1007/82_2018_129.BooksConceptsActivity-based protein profilingHost-pathogen interfaceProtein profilingFunctional proteomePathogen interactionsMicrobial pathogenicityComplex proteomesEnzyme-mediated mechanismReactive amino acidsActive enzymeChemical probesAmino acidsMetabolic adaptationProteomeMicrobial infectionsCo-culture systemBiological systemsHost immunityEnzymeProfilingPathogenicityHostProbeAnimal modelsAdaptation
2015
HaloPROTACS: Use of Small Molecule PROTACs to Induce Degradation of HaloTag Fusion Proteins
Buckley DL, Raina K, Darricarrere N, Hines J, Gustafson JL, Smith IE, Miah AH, Harling JD, Crews CM. HaloPROTACS: Use of Small Molecule PROTACs to Induce Degradation of HaloTag Fusion Proteins. ACS Chemical Biology 2015, 10: 1831-1837. PMID: 26070106, PMCID: PMC4629848, DOI: 10.1021/acschembio.5b00442.Peer-Reviewed Original ResearchConceptsChemical probesMore drug-like propertiesFusion proteinSmall-molecule PROTACsProtein degradationDrug-like propertiesE3 ligase ligandChemical genetic toolsSpecific E3 ligasesProtein of interestVHL ligandsHaloTag fusion proteinsE3 ligasesGenetic toolsHeterobifunctional moleculesNumerous proteinsHaloPROTACLigandsPROTACsProteinNovel classAttractive strategyDegradationProbeLigasesChemical Probes Reveal an Extraseptal Mode of Cross-Linking in Staphylococcus aureus
Gautam S, Kim T, Spiegel DA. Chemical Probes Reveal an Extraseptal Mode of Cross-Linking in Staphylococcus aureus. Journal Of The American Chemical Society 2015, 137: 7441-7447. PMID: 26035224, DOI: 10.1021/jacs.5b02972.Peer-Reviewed Original ResearchConceptsCross-linking activityPenicillin-binding proteinsCell divisionPeptidoglycan synthesisCell wall biogenesisEnzyme cross-linking activityCell wall synthesisWall biogenesisModel organismsWall synthesisImportant human pathogenCell wallChemical probesEndogenous substratesHuman pathogensSpherical bacteriaPBP4Distinct modesPeripheral wallDivisionBiogenesisS. aureusOrganismsStaphylococcus aureusProtein
2012
Forward Chemical Genetics in Yeast for Discovery of Chemical Probes Targeting Metabolism
St.Onge R, Schlecht U, Scharfe C, Evangelista M. Forward Chemical Genetics in Yeast for Discovery of Chemical Probes Targeting Metabolism. Molecules 2012, 17: 13098-13115. PMID: 23128089, PMCID: PMC3539408, DOI: 10.3390/molecules171113098.Peer-Reviewed Original ResearchConceptsChemical geneticsChemical probesCellular metabolismDominant model organismChemical genetic screeningForward chemical geneticsHigh-throughput phenotypicDrug target identificationNormal cellular metabolismNew chemical probesHigher eukaryotesExperimental tractabilityModel organismsYeast SaccharomycesCellular processesIdeal organismNew druggable targetsMolecular biologyYeastDruggable targetsGeneticsDiseased statesOrganismsGenetic screeningMetabolism
2009
Chemical Dissection of an Essential Redox Switch in Yeast
Paulsen CE, Carroll KS. Chemical Dissection of an Essential Redox Switch in Yeast. Cell Chemical Biology 2009, 16: 217-225. PMID: 19230722, DOI: 10.1016/j.chembiol.2009.01.003.Peer-Reviewed Original ResearchConceptsSulfenic acidCell-permeable chemical probesSulfenic acid modificationCysteine sulfenic acid modificationTranscription factor Yap1Chemical probesCysteine oxidationRedox switchElectrostatic calculationsIntermolecular disulfide formationCharge distributionHydrogen peroxideAcid modificationNuclear accumulationIntermolecular disulfideConformational rearrangementsDisulfide formationCentral unresolved questionYAP1 activationYAP1GPX3Chemical dissectionCatalysisUnresolved questionsAcidAn AlphaScreen™-Based High-Throughput Screen to Identify Inhibitors of Hsp90-Cochaperone Interaction
Yi F, Zhu P, Southall N, Inglese J, Austin CP, Zheng W, Regan L. An AlphaScreen™-Based High-Throughput Screen to Identify Inhibitors of Hsp90-Cochaperone Interaction. SLAS DISCOVERY 2009, 14: 273-281. PMID: 19211782, PMCID: PMC3066041, DOI: 10.1177/1087057108330114.Peer-Reviewed Original ResearchConceptsImportant anticancer drug targetFirst high-throughput screenHigh-throughput screenChemical probesNovel anticancer drugsAnticancer drug targetSuch moleculesAnticancer drugsTPR2A domainDifferent interactionsCompoundsSmall molecule Hsp90 inhibitorsNovel typeSynthetic peptidesFurther optimizationDrug targetsC-terminal peptideAlphaScreen technologyPeptidesDMSOReported valuesMoleculesInteractionHsp90 inhibitorsBackground ratio
2008
Expanding the Substrate Tolerance of Biotin Ligase through Exploration of Enzymes from Diverse Species
Slavoff SA, Chen I, Choi YA, Ting AY. Expanding the Substrate Tolerance of Biotin Ligase through Exploration of Enzymes from Diverse Species. Journal Of The American Chemical Society 2008, 130: 1160-1162. PMID: 18171066, PMCID: PMC3501195, DOI: 10.1021/ja076655i.Peer-Reviewed Original ResearchConceptsLigation reactionProtein labeling applicationsDifferential substrate specificitySite-specific conjugationBiotin acceptor domainPhosphine probesStaudinger ligationDiverse speciesBiotin ligaseChemical probesDifferent organismsMass spectrometry assayPyrococcus horikoshiiSubstrate specificityCell biologyUnnatural analoguesLabeling applicationsAcceptor domainsSubstrate toleranceLigasesDifferent speciesSpectrometry assayReactionSpeciesBiotin
2006
Substrate Profiling of Cysteine Proteases Using a Combinatorial Peptide Library Identifies Functionally Unique Specificities*
Choe Y, Leonetti F, Greenbaum DC, Lecaille F, Bogyo M, Brömme D, Ellman JA, Craik CS. Substrate Profiling of Cysteine Proteases Using a Combinatorial Peptide Library Identifies Functionally Unique Specificities*. Journal Of Biological Chemistry 2006, 281: 12824-12832. PMID: 16520377, DOI: 10.1074/jbc.m513331200.Peer-Reviewed Original ResearchConceptsIndividual peptide substratesSubstrate specificitySpecificity profilePeptide substratesSelective chemical probesPositional scanning synthetic combinatorial librariesStandard sequence analysisSimilar substrate specificityAmino acid preferencesSubstrate-based inhibitorsSynthetic combinatorial librariesCysteine protease papainThree-dimensional structureCleavage site sequenceFunctional characterizationChemical probesCoumarin fluorophoreFacilitated synthesisHuman cathepsin LPhysiological substratesSubstrate sequenceSite sequenceSequence analysisCysteine proteasesCombinatorial libraries
1999
Chemical genetics: exploring and controlling cellular processes with chemical probes
Crews C, Splittgerber U. Chemical genetics: exploring and controlling cellular processes with chemical probes. Trends In Biochemical Sciences 1999, 24: 317-320. PMID: 10431176, DOI: 10.1016/s0968-0004(99)01425-5.Peer-Reviewed Original Research
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