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.

WDR5是SET / MLL复合体的亚基，在各种生物学进展中起关键作用，并在许多癌症中异常表达。在这里，我们报告了一种捕获WDR5蛋白的新化学工具的设计，合成和生化特性。该探针是化合物30的生物素化版本，该化合物是我们之前报道的强效WDR5抑制剂。重要的是，该探针在体外显示出对WDR5蛋白的高亲和力结合力，并显示了特异性和实时监测WDR5蛋白的能力。此外，探针的生物素化标签可从MV4-11的全细胞裂解物中选择性“化学沉淀” WDR5。该探针提供了一种新的方法来鉴定在不同癌细胞中过表达的WDR5蛋白，并将其应用于WDR5和WDR5结合伴侣的蛋白质组学分析。