Conformational preferences of helix foldamers of [gamma]-peptides based on 2-(aminomethyl)cyclohexanecarboxylic acid

• Published in: Biopolymers Vol. 101; no. 1; pp. 87 - 95
• Main Authors: Byun, Byung Jin, Kang, Young Kee
• Format: Journal Article
• Language: English
• Published: 01.01.2014
• Subjects: Backbone; Biopolymers; Chloroform; Density; Dipole moment; Gas phases; Helical; Peptides
• ISSN: 0006-3525; 1097-0282
• DOI: 10.1002/bip.22287

The conformational preferences of helix foldamers having different sizes of the H-bonded pseudocycles have been studied for di- to octa-[gamma] super(2,3)-peptides based on 2-(aminomethyl)cyclohexanecarboxylic acid ([gamma]Amc sub(6)) with a cyclohexyl constraint on the C super([alpha])-C super([beta]) bond using density functional methods. The helical structures of the [gamma]Amc sub(6) 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)-2.5 sub(14)-helices are most preferred in the gas phase and in chloroform, whereas the (P/M)-2.3 sub(12)-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 [gamma]Amc sub(6) 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 [gamma]Amc sub(6) oligopeptides are quite similar to those of 2-aminocyclohexylacetic acid oligopeptides and [gamma] super(2,3,4)-aminobutyric acid tetrapeptide in the solid state, despite the different substituents on the backbone. [copy 2013 Wiley Periodicals, Inc. Biopolymers 101: 87-95, 2014.