2021
Recent Developments in PROTAC‐Mediated Protein Degradation: From Bench to Clinic
Hu Z, Crews CM. Recent Developments in PROTAC‐Mediated Protein Degradation: From Bench to Clinic. ChemBioChem 2021, 23: e202100270. PMID: 34494353, PMCID: PMC9395155, DOI: 10.1002/cbic.202100270.Peer-Reviewed Original Research
2001
Lack of Proteasome Active Site Allostery as Revealed by Subunit-Specific Inhibitors
Myung J, Kim K, Lindsten K, Dantuma N, Crews C. Lack of Proteasome Active Site Allostery as Revealed by Subunit-Specific Inhibitors. Molecular Cell 2001, 7: 411-420. PMID: 11239469, DOI: 10.1016/s1097-2765(01)00188-5.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric RegulationAnimalsBinding SitesCattleCell DivisionCells, CulturedChymotrypsinCysteine EndopeptidasesEndopeptidasesEpoxy CompoundsHumansHydrolysisKetonesKineticsModels, BiologicalMultienzyme ComplexesProtease InhibitorsProteasome Endopeptidase ComplexProtein SubunitsRecombinant Fusion ProteinsSerineSubstrate SpecificityTransfectionConceptsProtein degradation assaysSubunit-specific inhibitorsProtein degradationDegradation assaysCellular proliferationChymotrypsin-like activityPeptidyl-glutamyl peptideEpoxyketone inhibitorsActive siteSuch interactionsInhibitorsAllosteryProteasomeSitesSubunitsInhibitionSubstrateActivityProliferationAssaysPeptidesOccupancy
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 acidsSynthesisCompoundsComplexesEpoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity
Meng L, Mohan R, Kwok B, Elofsson M, Sin N, Crews C. Epoxomicin, a potent and selective proteasome inhibitor, exhibits in vivo antiinflammatory activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 10403-10408. PMID: 10468620, PMCID: PMC17900, DOI: 10.1073/pnas.96.18.10403.Peer-Reviewed Original ResearchAnimalsAntibiotics, AntineoplasticAnti-Inflammatory Agents, Non-SteroidalCattleCells, CulturedCysteine EndopeptidasesCysteine Proteinase InhibitorsEndothelium, VascularErythrocytesHeLa CellsHumansKineticsMultienzyme ComplexesOligopeptidesProteasome Endopeptidase ComplexTumor Cells, CulturedTumor Suppressor Protein p53UbiquitinsUmbilical Veins
1998
The Antiproliferative Agent Didemnin B Uncompetitively Inhibits Palmitoyl Protein Thioesterase †
Meng L, Sin N, Crews C. The Antiproliferative Agent Didemnin B Uncompetitively Inhibits Palmitoyl Protein Thioesterase †. Biochemistry 1998, 37: 10488-10492. PMID: 9671519, DOI: 10.1021/bi9804479.Peer-Reviewed Original ResearchConceptsPalmitoyl-protein thioesterase 1GTP-binding proteinsDynamic protein palmitoylationDidemnin BPalmitoyl-protein thioesterasePalmitoyl proteinsProtein palmitoylationMembrane associationBaculoviral systemMyristoyl-CoAProduct bindsHa-rasBiochemical supportProteinEnzymatic activityBindingInhibition assaysDepalmitoylationPalmitoylationThioesteraseKinetic analysisInhibitionBindsRegulationUncompetitive mode
1997
The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2
Sin N, Meng L, Wang M, Wen J, Bornmann W, Crews C. The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 6099-6103. PMID: 9177176, PMCID: PMC21008, DOI: 10.1073/pnas.94.12.6099.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAminopeptidasesAnimalsAntibiotics, AntineoplasticBinding SitesCattleCyclohexanesFatty Acids, UnsaturatedHumansKineticsMammalsMetalloendopeptidasesMethionyl AminopeptidasesMolecular Sequence DataNeovascularization, PathologicO-(Chloroacetylcarbamoyl)fumagillolSaccharomyces cerevisiaeSequence AlignmentSequence Homology, Amino AcidSesquiterpenesConceptsMethionine aminopeptidaseMetAP-1MetAP-2Mammalian proteinsBlood vessel formationVegetative growthTNP-470New blood vessel formationPotent biological activitiesMolecular modeProteinFungal metabolitesVessel formationAnimal model studiesAminopeptidaseAnti-angiogenic compoundsDetailed pharmacological studiesBiological activityImportant targetFumagillinClinical trialsSolid tumorsPharmacological studiesNatural productsSaccharomyces
1994
GTP-dependent binding of the antiproliferative agent didemnin to elongation factor 1 alpha.
Crews CM, Collins JL, Lane WS, Snapper ML, Schreiber SL. GTP-dependent binding of the antiproliferative agent didemnin to elongation factor 1 alpha. Journal Of Biological Chemistry 1994, 269: 15411-15414. PMID: 8195179, DOI: 10.1016/s0021-9258(17)40692-2.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAnti-Infective AgentsCarrier ProteinsCattleChromatography, AffinityDepsipeptidesGuanosine TriphosphateHumansIndicators and ReagentsKineticsMolecular Sequence DataPeptide Elongation Factor 1Peptide Elongation FactorsPeptides, CyclicProtein Synthesis InhibitorsSequence Homology, Amino AcidConceptsEF-1 alphaPotential antineoplastic drugElongation factor 1 alphaDidemnin BProtein synthesisAntiproliferative activityG1 cell cycle progressionGTP-dependent bindingFactor 1 alphaClinical trialsCell cycle progressionImmunosuppressive activityAntineoplastic drugsPeptide sequence analysisElongation factorMode of actionUndefined mechanismPresence of GTPGTPase activityCycle progressionNanomolar concentrationsSequence analysisAlphaMarine natural productsIntracellular targets