Macrocyclic Design Strategies for Small, Stable Parallel β-Sheet Scaffolds

摘要

Cyclization is a powerful strategy for inducing antiparallel β-sheet secondary structure in relatively short peptide segments. Biological examples feature cyclization via the backbone, as seen in gramicidin S and θ-defensin, and cyclization via side chains (disulfide formation), as seen in tachyplesins and protegrins. These natural prototypes have inspired the use of cyclization in β-sheet design efforts aimed at both structural and functional goals. For example, both backbone and side chain cyclization have been used to generate peptides that serve as spectroscopic references for the β-sheet conformations adopted by flexible, linear peptides. Cyclic β-sheet scaffolds have provided a fruitful basis for development of peptides with a variety of biological activities, including antibiotics, vaccine epitopes, RNA ligands, and, perhaps most intriguingly, helix-mimetic inhibitors of protein-protein recognition.