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Conformational preferences of helix foldamers of γ-peptides based on 2-(aminomethyl)cyclohexanecarboxylic acid

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  • This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

ABSTRACT

The conformational preferences of helix foldamers having different sizes of the H-bonded pseudocycles have been studied for di- to octa-γ2,3-peptides based on 2-(aminomethyl)cyclohexanecarboxylic acid (γAmc6) with a cyclohexyl constraint on the Cα–Cβ bond using density functional methods. The helical structures of the γAmc6 oligopeptides with homochiral configurations are known to be much stable than those with heterochiral configurations in the gas phase and in solution (chloroform and water). In particular, it is found that the (P/M)−2.514-helices are most preferred in the gas phase and in chloroform, whereas the (P/M)−2.312-helices become most populated in water due to the larger helix dipole moments. As the peptide sequence becomes longer, the helix propensities of 14- and 12-helices are found to increase both in the gas phase and in solution. The γAmc6 peptides longer than octapeptide are expected to exist as a mixture of 12- and 14-helices with the similar populations in water. The mean backbone torsion angles and helical parameters of the 14-helix foldamers of γAmc6 oligopeptides are quite similar to those of 2-aminocyclohexylacetic acid oligopeptides and γ2,3,4-aminobutyric acid tetrapeptide in the solid state, despite the different substituents on the backbone. © 2013 Wiley Periodicals, Inc. Biopolymers 101: 87–95, 2014.

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