Trapping a folding intermediate of the α-helix: Stabilization of the π-helix

We report the design, synthesis, and characterization of a short peptide trapped in a π-helix configuration. This high-energy conformation was nucleated by a preorganized π-turn, which was obtained by replacing an N-terminal intramolecular main chain i and i + 5 hydrogen bond with a carbon-carbon bond. Our studies highlight the nucleation parameter as a key factor contributing to the relative instability of the π-helix and allow us to estimate fundamental helix-coil transition parameters for this conformation.