In vitro expression of macrocyclic peptides

该项目旨在开发一种新的策略，用于生产多肽与非自然的化学基团使用义密码子重分配方法。新型多肽可用于一系列的制药应用。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扩展，但它们的位点选择性结合方法效率低下。该项目的策略依赖于从体外蛋白质翻译系统中消耗选定的trna，并用带有非天然氨基酸的合成trna替代。该技术有望用于快速生成和筛选高度多样化的大环肽库。

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.