Helix-forming aliphatic homo-δ-peptide foldamers based on the conformational restriction effects of cyclopropane. Issue 5 (25th November 2022)

• Record Type: Journal Article
• Authors: Nagata, Makoto; Watanabe, Mizuki; Doi, Ryohei; Uemura, Mai; Ochiai, Nanase; Ichinose, Wataru; Fujiwara, Koichi; Sato, Yoshihiro; Kameda, Tomoshi; Takeuchi, Koh; Shuto, Satoshi
• Is Part Of: Organic & biomolecular chemistry. Volume 21:Issue 5(2023)
• Page Start: 970
• Page End: 980
• Publication Date: 2022-11-25
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d2ob01715f
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : This work reports the first aliphatic homo-δ-peptide helical foldamer consisting of a conformationally restricted δ-amino acid, where the structural characteristics of cyclopropane tightly control the backbone torsion angles. Abstract : Considerable effort has been directed toward developing artificial peptide-based foldamers. However, detailed structural analysis of δ-peptide foldamers consisting of only aliphatic δ-amino acids has not been reported. Herein, we rationally designed and stereoselectively synthesized aliphatic homo-δ-peptides forming a stable helical structure by using a chiral cyclopropane δ-amino acid as a monomer unit. Structural analysis of the homo-δ-peptides using circular dichroism, infrared, and NMR spectroscopy indicated that they form a stable 14-helical structure in solution. Furthermore, we successfully conducted X-ray crystallographic analysis of the homo-δ-peptides, demonstrating a right-handed 14-helical structure. This helical structure of the crystal was consistent with those predicted by theoretical calculations and those obtained based on NMR spectroscopy in solution. This stable helical structure is due to the effective restriction of the backbone conformation by the structural characteristics of cyclopropane. This work reports the first example of aliphatic homo-δ-peptide foldamers having a stable helical structure both in the solution and crystal states.