Development of the Dominant Rotor Technology for Drug Discovery

用于药物发现的主导转子技术的开发

• 批准号: 565585-2021
• 负责人: Yudin, Andrei
• 金额: $ 4.77万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Alliance Grants
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=722841
• 关键词: Development; Dominant; Rotor; Technology; Drug

This proposal leverages the recently developed technology aimed at conformation-activity studies and rarely visited conformations of complex rings. The primary focus is on macrocycles that are primarily composed of natural amino acid building blocks. While cyclic peptides have received a tremendous amount of attention over the years, their structures are not ideally suited for the development of biological probes and therapeutic agents. Our new method, recently reported in Nature Chemistry, provides a solution to this challenge. Paraza Pharma and Genentech are the two partner organizations on this application.Genentech is a large biotechnology company with a rich history of excellence in peptide science and peptide-based drugs. Genentech Inc. has invested in the Yudin group as an industry partner with the goal to advance the understanding of peptide science. Genentech Inc. aims to use the technology developed in the Yudin lab to access new tools towards the synthesis of conformationally-controlled peptide-based inhibitors of protein-protein interactions. Genentech's involvement would help the Yudin lab to develop a library of structurally diverse macrocycles with unique dominant rotor sub-structures, and assess their chemical, physical, and biological properties in a much shorter amount of time compared to what is typically expected in an academic setting. Paraza Pharma is a chemical sciences-based company with aims towards streamlining the drug discovery processes. The company will use Yudin's chemistry in order to incorporate imidazopyridines into dominant rotors, deploy their exciting benzocyclobutane amino acids, and guide us through construction of macrocyclic kinase inhibitors. Paraza will provide scientific expertise in process and analytical development, particularly with regard to the suitability of Yudin's building blocks in synthesis.

这一建议利用了最近开发的针对构象活性研究的技术，并且很少访问复杂环的构象。主要的关注点是主要由天然氨基酸组成的大环。虽然环肽多年来受到了极大的关注，但它们的结构并不理想地适合于开发生物探针和治疗剂。我们最近在《自然化学》上报道的新方法为这一挑战提供了解决方案。Paraza Pharma和Genentech是这项应用的两家合作组织。Genentech是一家大型生物技术公司，在多肽科学和多肽药物方面拥有丰富的卓越历史。基因泰克公司投资玉丁集团作为行业合作伙伴，目的是促进对多肽科学的理解。基因泰克公司的目标是利用尤丁实验室开发的技术，获得合成构象控制的基于多肽的蛋白质-蛋白质相互作用抑制剂的新工具。基因泰克的参与将帮助尤丁实验室开发一个具有独特主导旋翼子结构的结构多样化的大旋转库，并在比学术环境中通常预期的时间短得多的时间内评估它们的化学、物理和生物特性。Paraza Pharma是一家以化学科学为基础的公司，旨在简化药物发现过程。该公司将利用尤丁的化学原理，将咪唑并吡啶类化合物加入到主要的转子中，部署它们令人兴奋的苯环丁烷氨基酸，并指导我们构建大环激酶抑制剂。Paraza将提供工艺和分析开发方面的科学专业知识，特别是在尤丁的构建块在合成中的适用性方面。