敌手
小分子
染色质
侧链
戒指(化学)
立体化学
分子
翻译(生物学)
化学
抄写(语言学)
转录因子
计算生物学
结合位点
领域(数学分析)
生物
受体
生物化学
DNA
信使核糖核酸
基因
数学
数学分析
语言学
哲学
有机化学
聚合物
作者
Meixia Chen,Zhuowen Wang,Weiguo Li,Yi‐Chang Chen,Qi Xiao,Xianjin Shang,Xiaolei Huang,Wei Z,Xingyue Ji,Yanli Liu
标识
DOI:10.1016/j.bbagrm.2023.194962
摘要
Tudor domain-containing protein 3 (TDRD3) is involved in regulating transcription and translation, promoting breast cancer progression, and modulating neurodevelopment and mental health, making it a promising therapeutic target for associated diseases. The Tudor domain of TDRD3 is essential for its biological functions, and targeting this domain with potent and selective chemical probes may modulate its engagement with chromatin and related functions. Here we reported a study of TDRD3 antagonist following on our earlier work on the development of the SMN antagonist, Compound 1, and demonstrated that TDRD3 can bind effectively to Compound 2, a triple-ring analog of Compound 1. Our structural analysis suggested that the triple-ring compound bound better to TDRD3 due to its smaller side chain at Y566 compared to W102 in SMN. We also revealed that adding a small hydrophobic group to the N-methyl site of Compound 1 can improve binding. These findings provide a path for identifying antagonists for single canonical Tudor domain-containing proteins such as TDRD3 and SMN.
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