Automated high-throughput synthesis and biological evaluation of compound libraries

高通量化学文库筛选（HTS）仍然是现代药物发现的支柱。它可以允许快速识别针对新的治疗候选化合物和/或用于生物系统研究的化学探针。然而，这种方法的局限性是访问大型和化学多样化的文库，有机合成和纯化仍然是该过程的主要瓶颈。该项目将采用自动化方法进行合成和筛选，避免了繁琐的纯化。我们将开发一个设计良好的构建块的小库，能够通过迭代耦合化学组装成更大的实体。结合机器人支持的高通量合成、固相合成和头上目标筛选的优势，我们的文库可以从合成直接到体外生物测试。这些方法将针对蛋白质-蛋白质相互作用抑制剂的发现，旨在显着简化它们的发现。

High-throughput chemical library screening (HTS) still forms the backbone of modern drug discovery. It can allow the rapid identification of hit compounds towards novel therapeutic candidates and/or chemical probes for the study of biological systems. However, the limitation of this methodology is access to large and chemically diverse libraries with organic synthesis and purification still being a major bottleneck in the process. This project will take an automated approach to both synthesis and screening, avoiding troublesome purification. We will develop a small library of well-designed building blocks capable of assembly into larger entities through iterative coupling chemistries. Combining the advantages of robotically enabled high-throughput synthesis, solid-phase synthesis and on-bead target screening our libraries can be taken from synthesis directly to in vitro biological testing. These approaches will be targeted towards the discovery of inhibitors for protein-protein interaction, aiming to significantly streamline their discovery.