The Sources, Synthesis, and Applications of Cyclopeptides

ABSTRACT Cyclic peptides, a class of highly constrained molecules generated through the closure of amino acid residues at their N‐ and C‐termini or side chains, have emerged as a focal point in the research of medicinal chemistry and materials science. This prominence is attributed to their remarkable stability, selectivity, and biological activity. This paper conducts a systematic review of the sources, synthetic strategies, and application progress of cyclic peptides across multiple domains. Initially, it summarizes the distribution and representative molecules of natural cyclic peptides in plants, microorganisms, and marine organisms, highlighting their structural diversity and pharmacological potential. Subsequently, it centers on the chemical synthesis methods of cyclic peptides, encompassing head‐to‐tail cyclization, side‐chain cyclization, and various non‐peptide bond construction strategies (such as disulfide bonds, thioether bonds, ester bonds, C─C bonds, and click chemistry bonds). It also compares the advantages of different approaches in terms of cyclization efficiency and conformational control. Finally, it outlines the recent application advancements of cyclic peptides in drug development, material design, food science, and bio‐diagnostics, demonstrating their extensive prospects in multidisciplinary research. The objective of this paper is to offer a theoretical basis and research reference for the structural optimization and functional design of cyclic peptides.