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.

该项目旨在开发一种使用有义密码子重新分配方法生产具有非天然化学基团的多肽的新策略，该方法可用于多种药物应用，由 20 种天然氨基酸组成的肽仅涵盖其中的一小部分。虽然肽的功能可以用非天然氨基酸来扩展，但该项目的策略依赖于所选氨基酸的耗尽。来自体外蛋白质翻译系统的 tRNA 及其用含有非天然氨基酸的合成 tRNA 的替代，预计所开发的技术可用于快速生成和筛选高度多样化的大环肽库。