小脑
泛素
泛素蛋白连接酶类
泛素连接酶
蛋白酶体
蛋白质水解
蛋白质降解
细胞生物学
化学
泛素类
融合蛋白
生物化学
生物
重组DNA
基因
酶
作者
Britton Ody,Jing Zhang,Sydney E. Nelson,Yayun Xie,Ruochuan Liu,Cayden J. Dodd,Savannah E. Jacobs,Savannah L. Whitzel,L. Williams,Samer Gozem,Mark Turlington,Jun Yin
出处
期刊:ChemBioChem
[Wiley]
日期:2023-08-25
卷期号:24 (21)
被引量:3
标识
DOI:10.1002/cbic.202300498
摘要
Target validation is key to the development of protein degrading molecules such as proteolysis-targeting chimeras (PROTACs) to identify cellular proteins amenable for induced degradation by the ubiquitin-proteasome system (UPS). Previously the HaloPROTAC system was developed to screen targets of PROTACs by linking the chlorohexyl group with the ligands of E3 ubiquitin ligases VHL and cIAP1 to recruit target proteins fused to the HaloTag for E3-catalyzed ubiquitination. Reported here are HaloPROTACs that engage the cereblon (CRBN) E3 to ubiquitinate and degrade HaloTagged proteins. A focused library of CRBN-pairing HaloPROTACs was synthesized and screened to identify efficient degraders of EGFP-HaloTag fusion with higher activities than VHL-engaging HaloPROTACs at sub-micromolar concentrations of the compound. The CRBN-engaging HaloPROTACs broadens the scope of the E3 ubiquitin ligases that can be utilized to screen suitable targets for induced protein degradation in the cell.
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