Comparison of design strategies for promotion of β-peptide 14-helix stability in water

Esther Vaz, William C. Pomerantz, Matthias Geyer, Samuel H. Gellman, Luc Brunsveld

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Many short β-peptides adopt well-defined conformations in organic solvents, but specialized stabilizing elements are required for folding to occur in aqueous solution. Several different strategies to stabilize the 14-helical secondary structure in water have been developed, and here we provide a direct comparison of three such strategies. We have synthesized and characterized β-peptide heptamers in which variously a salt bridge between side chains, a covalent link between side chains, or two cyclically constrained residues have been incorporated to promote 14-helicity. The incorporation of a salt bridge does not generate significant 14-helicity in water, according to CD and 2D NMR data. In contrast, incorporation either of a lactam bridge between side chains or of cyclic residues results in stable 14-helices in water. The β-peptides featuring trans-2-aminocyclohexanecarboxylic acid (ACHC) residues show the highest 14-helical backbone stability, with hardly any sensitivity to pH or ionic strength. The β-peptides featuring side-chain-to-side-chain cyclization show lower 14-helical backbone stability and higher sensitivity to pH and ionic strength, but increased order between the side chains because of the cyclization.

Original languageEnglish (US)
Pages (from-to)2254-2259
Number of pages6
Issue number14
StatePublished - Sep 22 2008


  • 14-helices
  • Beta-peptides
  • Conformation analysis
  • Cyclic peptides
  • Foldamers

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