Thioamide ligations: new technologies for peptide and protein synthesis

硫代酰胺连接：肽和蛋白质合成的新技术

• 批准号: DP190102509
• 负责人: Prof Craig Hutton
• 金额: $ 29.49万
• 依托单位: The University of Melbourne
• 依托单位国家: 澳大利亚
• 项目类别: Discovery Projects
• 财政年份: 2019
• 资助国家: 澳大利亚
• 起止时间: 2019-01-14 至 2023-03-31
• 项目状态: 已结题
• 来源: https://dataportal.arc.gov.au/RGS/Web/Grants/DP190102509
• 关键词: Thioamide; ligations; new; technologies; peptide

This project aims to develop novel amide-bond forming reactions for the chemical synthesis of peptides and proteins. New peptide ligation strategies, including an asparagine-based ligation and a residue-independent ligation will be developed that exploit the recent discovery of silver-promoted coupling reactions of thioamides. A novel late-stage, chemo-selective assembly of N-glycosylated asparagine residues in peptides and proteins will also be developed. The outcomes of this research will lead to breakthroughs in synthetic methodologies for the assembly and functionalisation of peptides and proteins, thereby enabling access to a range of homogeneous, post translationally modified proteins though total chemical synthesis. These research outcomes will expand Australia's research capability and global competitiveness in the field of biotechnology, delivering significant benefits to the third largest manufacturing sector in Australia.

该项目旨在开发用于化学合成肽和蛋白质的新型酰胺键形成反应。新的肽连接策略，包括基于天冬酰胺的连接和残基独立的连接将开发利用最近发现的银促进的硫代酰胺偶联反应。还将开发肽和蛋白质中N-糖基化天冬酰胺残基的新型后期化学选择性组装。该研究成果将在多肽和蛋白质组装和功能化的合成方法上取得突破，从而能够通过全化学合成获得一系列同质的、后修饰的蛋白质。这些研究成果将扩大澳大利亚在生物技术领域的研究能力和全球竞争力。为澳大利亚第三大制造业带来巨大利益。