A practical “preTACs-cytoblot” platform accelerates the streamlined development of PROTAC-based protein degraders
作者:Zijian Rao、Kailin Li、Ju Hong、Danni Chen、Baoli Ding、Li Jiang、Xuxin Qi、Jiawen Hu、Bo Yang、Qiaojun He、Xiaowu Dong、Ji Cao、Cheng-Liang Zhu
DOI:10.1016/j.ejmech.2023.115248
日期:2023.5
protein of interest to generate libraries of chimeric degraders, which are subsequently screened for effective protein degradation directly from cultured cells with a cytoblot assay. Our study exemplifies that this practical “preTACs-cytoblot” platform allows efficient PROTAC assembly and rapid activity assessments. It may help industrial and academic investigators to accelerate their streamlined development
随着 PROTAC 介导的蛋白质降解在药物发现中的重要性越来越大,迫切需要稳健的合成方法和快速筛选分析。通过利用改进的烯烃叠氮化反应,我们开发了一种将叠氮基引入接头-E3 配体偶联物的新策略,并有效地创建了一系列预包装的末端叠氮化物标记的“preTAC”作为 PROTAC 工具包构建块。此外,我们证明 preTAC 已准备好与靶向目标蛋白质的配体结合,以生成嵌合降解物文库,随后使用细胞印迹法直接从培养的细胞中筛选有效的蛋白质降解。我们的研究表明,这种实用的“preTACs-cytoblot”平台可以实现高效的 PROTAC 组装和快速的活性评估。