Lysine-targeting covalent inhibitors

该博士生将利用基于结构的合理设计，用赖氨酸靶向亲电试剂修饰突变体EGFR和突变体B-Raf的高亲和力可逆配体。然后，学生将使用生化方法来表征它们的抑制剂，以建立动力学参数，并与野生型蛋白质进行比较。然后将这些抑制剂应用于癌细胞，以建立激酶组选择性、脱靶反应性和野生型/突变型细胞治疗指数。

The PhD student will modify high affinity reversible ligands of mutant EGFR and mutant B-Raf with lysine-targeting electrophiles using structure based rational design. The student would then characterise their inhibitors using biochemical methods to establish kinetic parameters and compare with the wild-type proteins. The inhibitors would then be applied to cancer cells to establish kinome selectivity, off-target reactivity and wild-type/mutant cell therapeutic index.