Activity-directed synthesis toolkit

活性导向合成工具包

• 批准号: 1799580
• 金额: --
• 依托单位: University of Leeds
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1799580
• 关键词: Activity; directed; synthesis; toolkit

Activity-directed synthesis (ADS) is a novel discovery approach in which bioactive small molecules emerge in parallel with an associated synthetic route. The approach deliberately exploits reactions with many possible outcomes. Reaction arrays are performed in plate-based format, and the crude product mixtures are assayed for biological activity. Promising reactions then inform the design of reaction arrays in subsequent rounds. Finally, optimised reactions are scaled up, and the bioactive products are purified, structurally elucidated and functionally characterised. This iCASE project (in collaboration with GSK) will focus on expansion of the reaction toolkit for ADS to enable scaffold hopping. The new chemical tools will be exploited in the ADS of small molecule modulators of exemplar protein targets. The project focuses on the development of a new chemical approach to drive ligand discovery, and aligns with the EPSRC's chemical biology research area.

活性导向合成（ADS）是一种新的发现方法，其中生物活性小分子与相关的合成路线平行出现。这种方法故意利用具有许多可能结果的反应。反应阵列以基于板的形式进行，并测定粗产物混合物的生物活性。有希望的反应，然后通知在随后的几轮反应阵列的设计。最后，优化的反应被放大，生物活性产物被纯化，结构解析和功能表征。该iCASE项目（与GSK合作）将专注于扩展ADS的反应工具包，以实现支架跳跃。新的化学工具将在示例性蛋白质靶标的小分子调节剂的ADS中被利用。该项目的重点是开发一种新的化学方法来驱动配体的发现，并与EPSRC的化学生物学研究领域保持一致。