Enhancement of the Helical Content and Stability Induced in a Linear Oligopeptide by an i, i+4 Intramolecularly Double Stapled, Overlapping, Bicyclic [31,22,5]-(E)ene Motif

Two consecutive i, i+4 intramolecular, side chain to side chain, macrocyclizations of different type carried out on a preformed, partially helical peptide result in a largely predominant, double stapled, overlapping bicyclic [31,22,5]-(E)ene motif. A detailed ECD and NMR conformational study revealed a significant enhancement of the original helical content and stability, accompained by an increase of the alpha-helix amount over that of the 3(10)-helix.