Enzymatic Approaches for Next Generation Peptide Synthesis

下一代肽合成的酶法

• 批准号: EP/Y023714/1
• 负责人: Jason Micklefield
• 金额: $ 23.84万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FY023714%2F1
• 关键词: Enzymatic; Approaches; Next; Generation; Peptide

Solid phase peptide synthesis (SPPS), first introduced by Merrifield in 1963, revolutionised the way we make peptides and other biopolymers, inspired the development of combinatorial chemistry as well as automated chemical synthesis. The impact of this technology has been enormous, leading to the development of many new lifesaving pharmaceuticals and other materials of great value to society. Despite the tremendous importance of SPPS in science today, the basic principles and technology have not advanced greatly since it was first introduced. Moreover, current SPPS involves the use of large amounts of deleterious reagents and solvents that are damaging to the environment. ENGPEP will provide the first viable alternative enzymatic approaches for more sustainable peptide synthesis, using bespoke engineered ligase enzymes to couple amino acids and other precursors in the absence of protecting groups and other deleterious reagents. The provision of enzymatic methods for peptide synthesis would be a step change and could offer many applications including the cleaner and more efficient production of important and widely used peptide-based pharmaceuticals.

固相肽合成（SPPS），首先由梅里菲尔德在1963年推出，彻底改变了我们制造肽和其他生物聚合物的方式，启发了组合化学以及自动化学合成的发展。这项技术的影响是巨大的，导致了许多新的救生药物和其他对社会具有巨大价值的材料的开发。尽管SPPS在当今科学中具有巨大的重要性，但其基本原理和技术自首次引入以来并没有取得很大进展。此外，目前的SPPS涉及使用大量对环境有害的有害试剂和溶剂。ENGPEP将为更可持续的肽合成提供第一种可行的替代酶促方法，使用定制的工程连接酶在不存在保护基团和其他有害试剂的情况下偶联氨基酸和其他前体。提供用于肽合成的酶促方法将是一个步骤变化，并且可以提供许多应用，包括更清洁和更有效地生产重要和广泛使用的基于肽的药物。