Peptiligase, an enzyme for efficient chemo-enzymatic synthesis of aviptadil

Abstract

Increasing attention to peptides as prospective therapeutics has created a renaissance in searching for new alternatives to the current peptide synthetic approaches as well as their modification. In this context, it is necessary to develop different approaches for peptide ligation. Using enzymes as a novel strategy and powerful tool for the peptide and protein ligation has recently received a lot of attention. We here designed a fully convergent chemo-enzymatic peptide synthesis (CEPS) process for the synthesis of aviptadil a 28-mer therapeutic peptide with potential therapeutic effects in various medical contexts specially in the treatment of acute respiratory distress syndrome (ARDS) by coupling two peptide segments with four different peptiligase variants in aqueous environments. Our study reveals that peptiligase variants are capable of ligation reaction in 15 min. The overall time of ligation is shorter than those peptides with similar lengths and hinderance to aviptadil which reported for conventional synthesis by full solid-phase peptide synthesis. Yields ranged from 54 % to 76 %.