On the Cyclization of Non‐cyclic Peptides for Biological Applications: Inspiration from Naturally Cyclic Peptides

Abstract Peptides are unique class of biomolecules for pharmaceutics and industries, given their structural features that can be applied to many approaches. Although their advantages are known, they suffer from some limitations that need to be overcome. Some disadvantages are peptidic conformations’ flexibility and susceptibility to proteolytic degradation. Research has been in a constant endeavor to provide solutions. The discovery of cyclic peptides in plants opened the door for new insights into peptide‐based applications. These peptides display high stability to physical and chemical conditions. They possess a wide range of biological activities. In addition, cyclic peptides shows enhanced activities compared to linear peptides. Thus, the idea of non‐cyclic peptide cyclization can be of great use in eliminating issues and improving peptide capabilities. Inspired by the naturally found cyclic peptides, many approaches for synthetic cyclization have been proposed. The current review provides an overall discussion of the available methods for cyclization, applications, and characterization techniques. The present review offers a unique source for colleagues newly exposed to the subject and on the verge of entering the field of cyclic peptides by providing an initiating step covering the essential points needed to be considered around peptide cyclization.