Abstract
Living organisms have evolved cyclic or multicyclic peptides and proteins with enhanced stability and high bioactivity superior to their linear counterparts for diverse purposes. Herein, we review recent progress in applying this concept to artificial peptides and proteins to exploit the functional benefits of these macrocycles. Not only have simple cyclic forms been prepared, numerous macrocycle variants, such as knots and links, have also been developed. The chemical tools and synthetic strategies are summarized for the biological synthesis of these macrocycles, demonstrating it as a powerful alternative to chemical synthesis. Its further application to therapeutic peptides/proteins has led to biomedicines with profoundly improved pharmaceutical performances. Finally, we present our perspectives on the field and its future developments.
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