Intramolecular Crosslinking of an Optically Inactive 3₁₀-Helical Peptide:  Stabilization of Structure and Helix Sense

Cooperative structural stabilization and the deceleration of chirality interconversion of an octapeptide helix are achieved by a single intramolecular side-chain crosslinking, as revealed by X-ray crystallography, ¹H NMR spectroscopy, and computational analyses. The helical inversion is slow on the NMR time scale even at 80 °C. This is the first case of decelerated chirality inversion for helices based on the biological backbone, and the sequence -Api-Aib₂-Api- bridged with p-phenylenediacetic acid may serve as a key structural unit for the design of optically active peptides composed of only achiral building blocks and/or a variety of peptides with enhanced structural rigidity.