Specifications

Small molecule-induced protein degradation is an attractive strategy for the development of chemical probes. Protein degraders have the power to abrogate all of the functions of a drug target at once, including scaffolding functions which are difficult to target with small molecule inhibitors. A novel class of PROTACs that incorporate small molecule VHL ligands to successfully degrade HaloTag7 fusion proteins is developed. HaloPROTACs will inspire the development of future PROTACs with more drug-like properties. In HEK 293 cells stably expressing GFP-HaloTag7, 24 hour treatment with HaloPROTAC1 leads to less than 20% degradation, the longer HaloPROTAC2 leads to nearly 70% degradation of GFP-Halotag7 at 2.5 μM. HaloPROTACs containing 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 VHL as the E3 ubiquitin ligase component. Supplied with a primary amine functional handle at a position known not to significantly affect binding to VHL, for ready conjugation to a linker/target protein ligand.

Product Information:

Purity:                                   >98%MW:                                       467.02Formula:                               C22H31ClN4O3SCAS No.                                 1448189-80-7Physical State:                      Lyophilized white powderQuantity:                              5 mg; 10 mg; 25 mgSolubility:                             40 mg/mL in DMSOStorage:                                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.

References

1. Buckley DL et al. HaloPROTACS: Use of Small Molecule PROTACs to Induce Degradation of HaloTag Fusion Proteins. ACS Chem Biol. 2015 Aug 21;10(8):1831-7.2. Zengerle et al (2015) Selective small molecule induced degradation of the BET bromodomain protein BRD4. ACS Chem.Biol. 10 1770 PMID: 260356253. Galdeano et al (2014) Structure-guided design and optimization of small molecules targeting the protein-protein interaction between the von Hippel-Lindau (VHL) E3 ubiquitin ligase and the hypoxia inducible factor (HIF) alpha subunit with in vitro nanomolar affinities. J.Med.Chem. 57 8657

Life Sensors的泛素和泛素链泛素是一种小的多肽，通过其C端与目标蛋白上的赖氨酸的ε-氨基缀合。这种缀合称为单泛素化。随后，可以利用遍在蛋白表面上的七个赖氨酸残基（K6，K11，K27，K29，K33，K48，K63）中的任何一个，将额外的遍在蛋白部分与初始遍在蛋白结合。这种泛素链形成称为多泛素化。泛素的酶结合是通过一系列酶进行的，即泛素激活酶E1，泛素结合酶E2和泛素连接酶E3。蛋白质的泛素化在细胞中是可逆的。单泛素化和多泛素化的链均被去泛素化酶催化的水解作用裂解 （DUB）。LifeSensors在遍在泛素途径的所有水平的酶（包括E1，E2和E3酶和DUB）上都有丰富的经验。LifeSensors对蛋白质纯化的广泛了解使我们能够生产大约30种E2酶，20种E3酶和35个DUB，并具有定制表达的能力。此外，我们广泛的检测方法简化了确认酶活性和确定E2-E3对兼容性的过程，并确保您可以选择最能解决希望探索的特定，关键生物学问题的酶。LifeSensors已为您的研究开发了多种泛素衍生物，包括用于结合相互作用研究的DUB耐药性聚泛素链，用于DUB分析和筛选的泛素结合物（荧光团和报告酶），选择性泛素链（二，三和四环素）泛素链）用于DUB特异性和结合测定，位点特异性赖氨酸泛素突变体用于E3连接酶和DUB选择性测定。