2014
Small‐Molecule Control of Intracellular Protein Levels through Modulation of the Ubiquitin Proteasome System
Buckley DL, Crews CM. Small‐Molecule Control of Intracellular Protein Levels through Modulation of the Ubiquitin Proteasome System. Angewandte Chemie International Edition 2014, 53: 2312-2330. PMID: 24459094, PMCID: PMC4348030, DOI: 10.1002/anie.201307761.Peer-Reviewed Original ResearchConceptsSmall molecule modulatorsProtein levelsSmall-molecule probesUbiquitin-proteasome systemActivity of proteinsIntracellular protein levelsBiological probesProteasome systemProtein degradationUbiquitin-proteasomeProtein activitySmall moleculesMolecule controlDruggable targetsProteomeProteasomeTargeted fashionProteinRemaining majorityGlobal increaseProbeUPSMoleculesDegradationMultiple strategies
2010
Targeting the Undruggable Proteome: The Small Molecules of My Dreams
Crews CM. Targeting the Undruggable Proteome: The Small Molecules of My Dreams. Cell Chemical Biology 2010, 17: 551-555. PMID: 20609404, PMCID: PMC2925121, DOI: 10.1016/j.chembiol.2010.05.011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDrug DesignGeneticsHigh-Throughput Screening AssaysHumansProteomeSmall Molecule LibrariesConceptsTraditional genetic screensGenetic screenSmall moleculesUndruggable proteomeChemical genetic approachActive small moleculesSmall druglike moleculesSmall molecule librariesAreas of biologyChemical geneticsOrganismal levelDruglike moleculesDrug development effortsGenetic approachesCell biologyPharmaceutical interestBiological processesMolecule librariesPhenotypic changesMoleculesProteomeEarlier compoundsBiologyScreenNew bioassay
2006
Probing Protein Function with Small Molecules
Gough JD, Crews CM. Probing Protein Function with Small Molecules. Ernst Schering Foundation Symposium Proceedings 2006, 58: 61-74. PMID: 16708999, DOI: 10.1007/978-3-540-37635-4_5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiotinylationCombinatorial Chemistry TechniquesDrug DesignDrug Evaluation, PreclinicalGenomicsGreen Fluorescent ProteinsHumansKetonesModels, ChemicalMolecular Probe TechniquesNanotechnologyOligopeptidesPhosphorylationProtein BindingProteinsReceptors, AndrogenRecombinant Fusion ProteinsSerineSesquiterpenesSignal TransductionUbiquitin-Protein Ligases
1999
Towards subunit-specific proteasome inhibitors: synthesis and evaluation of peptide α', β'-epoxyketones
Elofsson M, Splittgerber U, Myung J, Mohan R, Crews C. Towards subunit-specific proteasome inhibitors: synthesis and evaluation of peptide α', β'-epoxyketones. Cell Chemical Biology 1999, 6: 811-822. PMID: 10574782, DOI: 10.1016/s1074-5521(99)80128-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaCattleCell DivisionCells, CulturedChymotrypsinCysteine EndopeptidasesCysteine Proteinase InhibitorsDrug DesignEndothelium, VascularEpoxy CompoundsGlutamatesIndicators and ReagentsIrritantsKineticsMacromolecular SubstancesMiceMolecular ConformationMultienzyme ComplexesPeptidesProteasome Endopeptidase ComplexTrypsinConceptsCatalytic activityMolecular probesAcetylated peptidesExcellent selectivityPotent proteasome inhibitorVivo anti-inflammatory activityMost compoundsMajor catalytic activityChymotrypsin-like activityPeptide αAromatic amino acidsEpoxyketonesAminoP2-P4Multicatalytic protease complexPeptidesAnti-inflammatory activitySelectivityProbeLarge multicatalytic protease complexesProteasome inhibitorsAmino acidsSynthesisCompoundsComplexes