Enzymatic Approaches for Next Generation Peptide Synthesis

固相多肽合成(SPPS)由Merrifield于1963年首次提出，它彻底改变了我们制造多肽和其他生物聚合物的方式，启发了组合化学和自动化化学合成的发展。这项技术的影响是巨大的，导致了许多新的救命药物和其他对社会有重要价值的材料的开发。尽管SPPS在今天的科学中具有巨大的重要性，但自从它第一次被引入以来，其基本原理和技术并没有得到很大的进步。此外，目前的SPPS涉及使用大量有害的试剂和溶剂，对环境造成破坏。ENGPEP将为更可持续的多肽合成提供第一种可行的替代酶方法，使用定制的工程连接酶在没有保护基团和其他有害试剂的情况下将氨基酸和其他前体偶联。提供用于多肽合成的酶方法将是一个阶段性的变化，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多肽药物。

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.