12/10- and 11/13-mixed helices in α/γ- and β/γ-hybrid peptides containing C-linked carbo-γ-amino acids with alternating α- and β-amino acids

New classes of alpha/gamma- and beta/gamma-hybrid peptides have been synthesized with novel 12/10- and 11/13-mixed helical patterns, respectively. The alpha/gamma-peptides were derived from the dipeptide repeats with alternating arrays of L-Ala and gamma-Caa((l)) (C-linked carbo-gamma-amino acid from D-mannose), which generated a new 12/10-mixed helix, for the first time, without beta-amino acid. The beta/gamma-peptides made from an alternating arrangement of beta-Caa((x)) (C-linked carbo-beta-amino acid) and gamma-Caa((x)) (C-linked carbo-gamma-amino acid from D-xylose), on the other hand, resulted in an unprecedented 11/13-helix. The secondary structures in these peptides have been ascertained from detailed NMR studies, and CD spectroscopy and molecular dynamics investigations provided additional support for the structures derived.