Design, synthesis, and initial evaluation of affinity-based small molecular probe for detection of WDR5
Design, synthesis, and initial evaluation of affinity-based small molecular probe for detection of WDR5
复制标题
用于检测 WDR5 的基于亲和力的小分子探针的设计、合成和初步评估
DOI：
10.1016/j.bioorg.2017.11.018
复制
发表时间：
2018-02-01
影响因子：
5.1
通讯作者：
You, Qi-Dong
中科院分区：
文献类型：
--
作者：
Chen, Wei-Lin;Li, Dong-Dong;You, Qi-Dong
WDR5是SET/MLL复合体的一个亚基，在多种生物学过程中发挥关键作用，在许多癌症中异常表达。本文报道了一种捕获WDR5蛋白的新化学工具的设计、合成和生化表征。该探针是化合物30的生物素化版本，是我们之前报道的一种有效的WDR5抑制剂。重要的是，该探针显示出对WDR5蛋白的高亲和力和体外结合能力，显示出对WDR5蛋白的特异性和实时监测能力。此外，该探针的生物素化标签能够从MV4-11的全细胞裂解物中选择性地“化学沉淀”WDR5。该探针为鉴定不同肿瘤细胞中过表达的WDR5蛋白提供了新的途径，并可用于WDR5及其结合伙伴的蛋白质组学分析。(C) 2017年Elsevier Inc.出版。
WDR5, a subunit of the SET/MLL complex, plays critical roles in various biological progresses and are abnormally expressed in many cancers. Here we report the design, synthesis, and biochemical characterization of a new chemical tool to capture WDR5 protein. The probe is a biotinylated version of compound 30 that is a potent WDR5 inhibitor we previously reported. Importantly, the probe displayed high affinity to WDR5 protein in vitro binding potency and showed the ability in specifically and real time monitoring WDR5 protein. Further, the biotinylated tag of the probe enabled selectively "chemoprecipitation" of WDR5 from whole cell lysates of MV4-11. This probe provided a new approach to identify the overexpressed WDR5 protein in different cancer cells and applications to proteomic analysis of WDR5 and WDR5-binding partners. (C) 2017 Published by Elsevier Inc.