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


  • This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at

  • Y.B.H. and J.F.S. contributed equally to this work.


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, accompanied by an increase of the α-helix amount over that of the 310-helix. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 115–123, 2014.