Exploring Helical Folding in Oligomers of Cyclopentane-Based ϵ-Amino Acids: A Computational Study.

Abstract

The conformational preferences of oligopeptides of an ϵ‐amino acid (2‐((1R,3S)‐3‐(aminomethyl)cyclopentyl)acetic acid, Amc5a) with a cyclopentane substituent in the Cβ−Cγ−Cδ sequence of the backbone were investigated using DFT methods in chloroform and water. The most preferred conformation of Amc5a oligomers (dimer to hexamer) was the H16 helical structure both in chloroform and water. Four residues were found to be sufficient to induce a substantial H16 helix population in solution. The Amc5a hexamer adopted a stable left‐handed (M)‐2.316 helical conformation with a rise of 4.8 Å per turn. The hexamer of Ampa (an analogue of Amc5a with replacing cyclopentane by pyrrolidine) adopted the right‐handed mixed (P)‐2.918/16 helical conformation in chloroform and the (M)‐2.416 helical conformation in water. Therefore, hexamers of ϵ‐amino acid residues exhibited different preferences of helical structures depending on the substituents in peptide backbone and the solvent polarity as well as the chain length.