Development of the Dominant Rotor Technology for Drug Discovery

该建议利用了最近开发的技术，旨在构象活性研究和很少访问的复杂环的构象。主要关注的是主要由天然氨基酸结构单元组成的大环化合物。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生物探针和治疗剂的开发。我们最近在《自然化学》杂志上报道的新方法为这一挑战提供了解决方案。帕拉扎制药公司和基因泰克公司是这一申请的两个合作伙伴组织。基因泰克公司是一家大型生物技术公司，在肽科学和肽类药物方面有着丰富的卓越历史。Genentech Inc.已投资Yudin集团作为行业合作伙伴，旨在促进对肽科学的理解。Genentech Inc.旨在使用Yudin实验室开发的技术来获得新的工具，以合成蛋白质-蛋白质相互作用的构象控制肽基抑制剂。Genentech的参与将有助于Yudin实验室开发一个具有独特主导转子子结构的结构多样的大环化合物库，并在比学术环境中通常预期的更短的时间内评估其化学，物理和生物特性。帕拉扎制药公司是一家以化学科学为基础的公司，旨在简化药物发现过程。该公司将使用Yudin的化学方法将咪唑并吡啶纳入主导转子，部署其令人兴奋的苯并环丁烷氨基酸，并指导我们构建大环激酶抑制剂。帕拉扎将提供工艺和分析开发方面的科学专业知识，特别是关于Yudin的合成结构单元的适用性。

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.