Oral Presentation International Peptide Symposium 2023

Peptide Synthesis Using Unprotected Amino Acids (#115)

Junfeng Zhao 1
  1. Guangzhou Medical University, Guangzhou, GUANGDONG PROVINCE, China

Peptide therapeutics have witnessed a rapid renaissance over the past three decades[1]. The request for peptide active pharmaceutical ingredient (API) increases dramatically. Chemical peptide synthesis plays a mainstay role for peptide APIs manufacture because modifications are typically necessary to increase the half life time. However, the mandatory use of Nα-protecting group for amino acids in peptide synthesis results in poor step- and atom-economy[2]. More than one hundred atoms are wasted for constructing a single peptide bond, and metric tons of chemical waste are generated for producing each kilogram of peptide[3]. Atom-economic peptide bond formation has been identified as one of the top 10 challenges of green chemistry research area twice over the last two decades[4]. Furthermore, current peptide synthesis relies heavily on legacy technologies and reagents developed in the 1950s-1980s, before the establishment of green chemistry principles. Although a lot of efforts have been devoted to greening peptide synthesis, most of them just improved the reaction efficiency at technic level. Only the innovations in peptide synthesis principles can address the low atom-economic issue completely. Using unprotected amino acids as the building blocks for peptide synthesis represents an attractive and ideal strategy for greening peptide synthesis because it gets rid of protection and deprotection operations. Unfortunately, such strategy has been remained unsuccessful for more than 60 years because of severe racemization/epimerization encountered by conventional coupling reagents during N→C peptide elongation. Herein, we successfully addressed the notorious racemization/epimerization issue by employing ynamide[5a, 5b] or allenone[6] coupling reagents discovered by our research group. The first general green peptide synthesis by using unprotected amino acids as the building blocks have been reported[7].