Design of Helical Peptide Foldamers through α,β→ β,γ Double-Bond Migration

The direct transformation of nonhelical α,γ-hybrid peptides composed of alternating α- and E-vinylogous amino acids into 12-helical structures through a base-mediated α,β → β,γ double-bond migration is reported. The conformations of double-bond-migrated new 12-helices were studied in single crystals and in solution. Instructively, the 12-helices reported here were found to be acid labile, and they completely break down into the corresponding amino acid derivatives upon treatment with acids.