Small molecule tools to target glucose metabolism in non-alcoholic fatty liver disease

该项目与我们正在进行的设计和合成新型化学生物学工具分子以询问和调节葡萄糖激酶（GK）的努力相一致。这些化学探针将用于建立GK抑制作为NAFLD的治疗靶点。该项目将分为两个互补链，将平行进行：a）GK的新型蛋白水解靶向嵌合分子（PROTAC）的设计和合成将测试GK可靶向降解的假设; B）通过筛选纽卡斯尔FragLites文库进行GK蛋白质图谱分析，将评估GK的可药用性，并确定GK抑制是否可用小分子处理。该奖学金将提供丰富的药物化学设计和有机合成经验。这将是理想的培训，有人希望追求职业生涯中的药物化学或化学生物学。

The project is aligned to our ongoing efforts to design and synthesise novel chemical biology tool molecules to interrogate and modulate glucokinase enzyme (GK). These chemical probes will be used to establish GK inhibition as a therapeutic target in NAFLD. The project will be split into two complimentary strands which will be approached in parallel: a) the design and synthesis of novel proteolysis targeting chimeric molecules (PROTACs) of GK will test the hypothesis that GK can be targeted for degradation; b) the mapping of GK protein by screening the Newcastle FragLites library will assess GK druggability and establish whether GK inhibition is tractable with a small molecule. The studentship will provide a wealth of experience in medicinal chemistry design and organic synthesis. This would be ideal training for someone wishing to pursue a career in medicinal chemistry or chemical biology.