Smallmolecule-inducedproteindegradationisanattractivestrategyforthedevelopmentofchemicalprobes.Proteindegradershavethepowertoabrogateallofthefunctionsofadrugtargetatonce,includingscaffoldingfunctionswhicharedifficulttotargetwithsmallmoleculeinhibitors.AnovelclassofPROTACsthatincorporatesmallmoleculeVHLligandstosuccessfullydegradeHaloTag7fusionproteinsisdeveloped.HaloPROTACswillinspirethedevelopmentoffuturePROTACswithmoredrug-likeproperties.InHEK293cellsstablyexpressingGFP-HaloTag7,24hourtreatmentwithHaloPROTAC1leadstolessthan20%degradation,thelongerHaloPROTAC2leadstonearly70%degradationofGFP-Halotag7at2.5μM.HaloPROTACscontainingproteindegrader1leadstonearly70%degradationofGFP-HaloTag7,whensufficientlylonglinkersareused.DerivativeofthevonHippel-Lindau(VHL)ligand,VH032,commonlyusedasaprecursortoPROTACsthathijackVHLastheE3ubiquitinligasecomponent.SuppliedwithaprimaryaminefunctionalhandleatapositionknownnottosignificantlyaffectbindingtoVHL,forreadyconjugationtoalinker/targetproteinligand.
Application:
FunctionalizedVHLligandforPROTACs
ProductInformation:
Purity: >98%
MW: 467.02
Formula: C22H31ClN4O3S
CASNo. 1448189-80-7
PhysicalState: Lyophilizedwhitepowder
Quantity: 5mg;10mg;25mg
Solubility: 40mg/mLinDMSO
Storage: Storedesiccatedassuppliedat-20°Cforupto3years.Storesolutionsat-80°Cforupto6monthsor-20°Cforupto1month.
Documents
References
1. BuckleyDL etal.HaloPROTACS:UseofSmallMoleculePROTACstoInduceDegradationofHaloTagFusionProteins.ACSChemBiol.2015Aug21;10(8):1831-7.
2. Zengerle etal (2015)SelectivesmallmoleculeinduceddegradationoftheBETbromodomainproteinBRD4.ACSChem.Biol. 10 1770PMID: 26035625
3. Galdeano etal (2014)Structure-guideddesignandoptimizationofsmallmoleculestargetingtheprotein-proteininteractionbetweenthevonHippel-Lindau(VHL)E3ubiquitinligaseandthehypoxiainducIBLefactor(HIF)alphasubunitwith invitro nanomolaraffinities.J.Med.Chem. 57 8657
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那糖酵解中依赖NAD的酶不是要在线粒体内反应?
蛋白酶分布广泛,主要存在于人和动物消化道中,而消化道通过口与肛门与外界相通,属于外环境或外界环境
(溶菌酶、凝血酶原等)分布在内环境
(消化)酶分布在消化道

