Small molecule-induced protein degradation is anattractive strategy for the development of chemical probes. Protein degradershave the power to abrogate all of the functions of a drug target at once,including scaffolding functions which are difficult to target with smallmolecule inhibitors. A novel class of PROTACs that incorporate small moleculeVHL ligands to successfully degrade HaloTag7 fusion proteins is developed.HaloPROTACs will inspire the development of future PROTACs with more drug-likeproperties. In HEK 293 cells stably expressing GFP-HaloTag7, 24 hour treatmentwith HaloPROTAC1 leads to less than 20% degradation, the longer HaloPROTAC2leads to nearly 70% degradation of GFP-Halotag7 at 2.5 μM. HaloPROTACscontaining protein degrader 1 leads to nearly 70% degradation of GFP-HaloTag7,when sufficiently long linkers are used. Derivative of the von Hippel-Lindau(VHL) ligand, VH 032, commonly used as a precursor to PROTACs that hijack VHLas the E3 ubiquitin ligase component. Supplied with a primary amine functionalhandle at a position known not to significantly affect binding to VHL, forready conjugation to a linker/target protein ligand.
Application:
Functionalized VHL ligandfor PROTACs
Product Information:
Purity: >98%
MW: 467.02
Formula: C22H31ClN4O3S
CAS No. 1448189-80-7
Physical State: Lyophilized white powder
Quantity: 5 mg; 10 mg; 25 mg
Solubility: 40 mg/mL in DMSO
Storage: Store desiccated as supplied at -20°C for up to 3 years. Store solutions at -80°C for up to 6 months or -20°C for up to 1 month.
Documents
References
1. Buckley DL et al. HaloPROTACS: Use of Small Molecule PROTACsto Induce Degradation of HaloTag Fusion Proteins. ACS Chem Biol. 2015 Aug21;10(8):1831-7.
2. Zengerle et al (2015) Selective smallmolecule induced degradation of the BET bromodomain protein BRD4. ACSChem.Biol. 101770 PMID: 26035625
3. Galdeano et al (2014) Structure-guideddesign and optimization of small molecules targeting the protein-proteininteraction between the von Hippel-Lindau (VHL) E3 ubiquitin ligase and thehypoxia inducible factor (HIF) alpha subunit with in vitro nanomolar affinities. J.Med.Chem. 57 8657
ebiomall.com
>
>
>
>
>
>
>
>
>
>
>
>
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
