In vitro expression of macrocyclic peptides

大环肽的体外表达

• 批准号: LP150100689
• 负责人: Prof Kirill Alexandrov
• 金额: $ 46.63万
• 依托单位: Queensland University of Technology
• 依托单位国家: 澳大利亚
• 项目类别: Linkage Projects
• 财政年份: 2016
• 资助国家: 澳大利亚
• 起止时间: 2016-06-27 至 2020-12-31
• 项目状态: 已结题
• 来源: https://dataportal.arc.gov.au/RGS/Web/Grants/LP150100689
• 关键词: vitro; expression; macrocyclic; peptides

This project aims to develop a novel strategy for the production of polypeptides with unnatural chemical groups using a sense codon reassignment approach. Novel peptides could be used in a range of pharmaceutical applications. Peptides made of 20 natural amino acids cover only a very small fraction of the available chemical and functional space. While a peptide’s functionality can be extended with unnatural amino acids, the methods for their site-selective incorporation are inefficient. The project’s strategy relies on the depletion of selected tRNAs from an in vitro protein translation system and their replacement with synthetic tRNAs, charged with unnatural amino acids. It is expected that the developed technology could be used to rapidly generate and screen highly diversified macrocyclic peptide libraries.

本计画旨在发展一种新的策略，利用正义密码子再分配的方法来生产具有非天然化学基团的多肽。新型肽可用于一系列药物应用中。由20种天然氨基酸组成的肽只占可用化学和功能空间的很小一部分。虽然肽的功能可以用非天然氨基酸延伸，但是用于它们的位点选择性掺入的方法是低效的。该项目的策略依赖于从体外蛋白质翻译系统中耗尽选定的tRNA，并用合成的tRNA取代它们，并加载非天然氨基酸。预计该技术可用于快速生成和筛选高度多样化的大环肽文库。