Considerable effort has been directed toward developing artificial peptide-based foldamers. To date, however, detailed structural analysis of δ-peptide foldamers consisting of aliphatic δ-amino acids has not been reported. Herein, we rationally designed and stereoselectively synthesized aliphatic homo-δ-peptide foldamers forming a stable helical structure utilizing a chiral cyclopropane δ-amino acid as a monomer unit. Structural analysis of the homo-δ-peptides revealed that they form a stable 14-helical structure in solution. Furthermore, we successfully achieved X-ray crystallographic analysis of the homo-δ-peptides, showing their common right-handed 14-helical structures. The critical point is that the helical structures of these δ-peptides are theoretically predictable by calculations. This is the first example of aliphatic homo-δ-peptide foldamers forming a stable helical structure both in solution and crystal.
Data of molecular dynamics (MD) simulations are added.
X-ray crystal structure of N-Ac-tetramer 11a