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 strategyDegradationProbeLigases
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
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 acidsSynthesisCompoundsComplexesChemical 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
1998
Eponemycin analogues: syntheses and use as probes of angiogenesis
Sin N, Meng L, Auth H, Crews C. Eponemycin analogues: syntheses and use as probes of angiogenesis. Bioorganic & Medicinal Chemistry 1998, 6: 1209-1217. PMID: 9784862, DOI: 10.1016/s0968-0896(98)00089-3.Peer-Reviewed Original Research