Identification and development of cyclic peptide libraries containing non-natural amino acids

含有非天然氨基酸的环肽文库的鉴定和开发

• 批准号: 2720738
• 金额: --
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2720738
• 关键词: Identification; development; cyclic; peptide; libraries

The aim of this project is to develop a high-throughput screening platform, that uses droplet microfluidics to co-encapsulate and screen a SICLOIPPS (split-intein circular ligation of peptides and proteins) library of 3.2 million cyclic peptides containing multiple non-natural amino acids. Once established, this platform will be used to identify inhibitors of a therapeutically relevant protein-protein interaction. This work builds on previous work form the Tavasoli lab whereby a library of 3.2 million cyclic peptides have been produced in fL double-emulsion droplets. A combination of chemical and biochemical methods will be used to charge tRNA with non-natural amino acids. The product of these reactions will be used in custom in vitro transcription and translation systems, enabling the production of SICLOPPS libraries containing multiple non-natural amino acids.

该项目的目的是开发一个高通量筛选平台，使用液滴微流控技术共封装和筛选包含 320 万个含有多种非天然氨基酸的环肽的 SICLOIPPS（肽和蛋白质的分裂内含肽环状连接）文库。一旦建立，该平台将用于识别治疗相关的蛋白质-蛋白质相互作用的抑制剂。这项工作建立在 Tavasoli 实验室之前的工作基础上，其中在 fL 双乳液液滴中生成了包含 320 万个环肽的库。将采用化学和生化方法相结合的方式为 tRNA 注入非天然氨基酸。这些反应的产物将用于定制的体外转录和翻译系统，从而能够产生含有多种非天然氨基酸的 SICLOPPS 文库。