Recent development in peptide coupling reagents

Two decades of domination of benzotriazole-based chemistry stimulated the progress in peptide synthesis to a high level of effectiveness. However, the growing need for new and more complex peptide structures, particularly for biomedical studies and, very recently, for the large-scale production of peptides as drugs, required manufacturing peptide products by efficient synthetic strategies, at reasonably low prices. Therefore, the search for new, more versatile and low-cost reagents becomes a great challenge. Several comprehensive review articles summarized the great effort undertaken, but up to now, no versatile coupling reagent useful for both amide and ester bond formation, as well as for solution and solid-phase peptide synthesis has been yet developed. The most-widely used coupling reagents are carbodiimides on one hand and phosphonium and aminium salts on the other. Herein in this review article, we summarized the recent development in peptide coupling reagents during the last two decades.