The structural and functional impacts of rationally designed cyclic peptides on self-assembly-mediated functionality.

Abstract

Compared with their linear counterparts, cyclic peptides, characterized by their unique topologies, offer superior stability and enhanced functionality. In this review article, the rational design of cyclic peptide primary structures and their significant influence on self-assembly processes and functional capabilities are comprehensively reviewed. We emphasize how strategically modifying amino acid sequences and ring sizes critically dictate the formation and properties of peptide nanotubes (PNTs) and complex assemblies, such as rotaxanes. Adjusting the number of amino acid residues and side chains allows researchers to tailor the diameter, surface properties, and functions of PNTs precisely. In addition, we discuss the complex host-guest chemistry of cyclic peptides and their ability to form rotaxanes, highlighting their potential in the development of mechanically interlocked structures with novel functionalities. Moreover, the critical role of computational methods for accurately predicting the solution structures of cyclic peptides is also highlighted, as it enables the design of novel peptides with tailored properties for a range of applications. These insights set the stage for groundbreaking advances in nanotechnology, drug delivery, and materials science, driven by the strategic design of cyclic peptide primary structures.