Non-classical Helices with cis Carbon-Carbon Double Bonds in the Backbone: Structural Features of α,γ-Hybrid Peptide Foldamers

• Published in: Angewandte Chemie (International ed.) Vol. 55; no. 27; pp. 7847 - 7851
• Main Authors: Ganesh Kumar, Mothukuri, Thombare, Varsha J., Katariya, Mona M., Veeresh, Kuruva, Raja, K. Muruga Poopathi, Gopi, Hosahudya N.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Blackwell Publishing Ltd 27.06.2016; Wiley
• Subjects: Chemistry; Chemistry, Multidisciplinary; foldamers; non-natural amino acids; peptide helices; peptides; Physical Sciences; Science & Technology; X-ray crystallography; DESIGN; BUILDING-BLOCKS; peptides; CD SPECTRA; BETA-PEPTIDES; foldamers; peptide helices; X-ray crystallography; PROTEINOGENIC SIDE-CHAINS; non-natural amino acids; X-RAY-CRYSTAL; ALPHA/GAMMA-HYBRID; NMR-SOLUTION; AMINO-ACID-RESIDUES; SECONDARY STRUCTURE
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201602861

The impact of geometrically constrained cis α,β‐unsaturated γ‐amino acids on the folding of α,γ‐hybrid peptides was investigated. Structure analysis in single crystals and in solution revealed that the cis carbon–carbon double bonds can be accommodated into the 12‐helix without deviation from the overall helical conformation. The helical structures are stabilized by 4→1 hydrogen bonding in a similar manner to the 12‐helices of β‐peptides and the 310 helices of α‐peptides. These results show that functional cis carbon–carbon double bonds can be accommodated into the backbone of helical peptides. Do the twist: The design, synthesis, and solution and single‐crystal conformations of hybrid helices containing cis carbon–carbon double bonds in the backbone are presented. The results reveal that cis double bonds can be accommodated into the helix without deviation from the overall helical fold.