Helix foldamers of γ-peptides based on 2-aminocyclopentylacetic acidElectronic supplementary information (ESI) available: Backbone torsion angles of optimized helical and extended structures of oligo-γAc5a peptides, mean distances and angles for H-bonds of helix foldamers, helical parameters of helix foldamers, optimized helical and extended structures and Cartesian coordinates of oligo-γAc5a peptides. See DOI: 10.1039/c4nj01202j

• Main Authors: Kang, Young Kee, Lee, Joo Yun
• Format: Journal Article
• Language: English
• Published: 06.05.2015
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/c4nj01202j

The conformational preferences of helix foldamers have been studied in oligo-γ-peptides composed of 2-aminocyclopentylacetic acid (γAc 5 a) with a cyclopentyl constraint on the C β -C γ bond using density functional methods. Although the γAc 5 a ( 1 ) dipeptide with homochiral (1 S ,2 S ) configurations exhibits a strong preference for the right-handed ( P ) 9-membered helix foldamer in chloroform and water, oligopeptides composed of γAc 5 a ( 1 ) preferentially adopt ( P )-2.5 14 -helices due to the favored conformational energy produced as the peptide sequence becomes longer and as solvent polarity increases. The calculated mean backbone torsion angles and helical parameters for 14-helical foldamers composed of γAc 5 a ( 1 ) are consistent with those measured in the X-ray structures of penta- and hexapeptides composed of C α -ethyl-γAc 6 a and 14-helical foldamers composed of γAc 6 a ( 1 ) with cyclohexyl constraints. However, the substitution of cyclopentane constraints in the backbone differentially changed the conformational preference and/or handedness for helix foldamers when compared with other oligo-γ-peptides with different cycloalkane positions or size constraints. The conformational preferences of the oligo-γAc 5 a peptides obtained here are expected to provide useful information for the structure-based design of biologically active γ-peptides with specific functions. Oligo-γ-peptides based on 2-aminocyclopentylacetic acid (γAc 5 a) with a cyclopentyl constraint on the C β -C γ bond and homochiral (1 S ,2 S ) configurations preferentially adopt the right-handed 14-helix foldamers in the gas phase and in solution.