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Updated: Aug 20, 2025

Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly
Published on: February 6, 2020
Helix-forming aliphatic homo-δ-peptide foldamers based on the conformational restriction effects of cyclopropane
Makoto Nagata1, Mizuki Watanabe1, Ryohei Doi1
1Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan. mwatanab@pharm.hokudai.ac.jp.
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.
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