Enzymatic Approaches for Next Generation Peptide Synthesis

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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.