Conformationally restricted peptides: solution conformation of tetra and hepta peptides containing α,β-dehydrophenylalanine residues in alternate positions

Abstract

Two model peptides containing dehydrophenylalanine, a tetrapeptide 1 (Ac- Δ^zPhe-Pro-Δ^zPhe-Ala-OMe) and a heptapeptide 2 (Boc-Gly-Δ^zPhe-Val-Δ^zPhe-Ala-Δ^zPhe-Leu-OMe) have been synthesised and their solution conformations investigated by NMR and circular dichroism techniques. Assignment of amide protons and their involvement in intramolecular hydrogen bonding have been made by solvent and temperature dependence studies. These conformation studies indicate the presence of an incipient 3₁₀-helix in tetrapeptide 1, with two consecutive β-turns and a right handed 3₁₀-helix in heptapeptide 2. The results establish the potential of Δ^zPhe residues to favour 3₁₀-helical conformations with δ^zPhe occupying alternate positions in the peptide. A comparison of solution conformation of analogous peptides containing Aib residue in place of Δ^zPhe is also presented. These residues appear to induce similar conformation constraints in small peptides.