Incorporation of a potentially helix-breaking D-Phe-Pro sequence into the center of a right-handed 16-residue peptide helix

Abstract

Non protein amino acids with strong secondary structure preferences are potentially useful in peptide design. ?-Aminoisobutyric acid (Aib) is a powerful ?stereochemical director' of polypeptide chain folding, stabilizing helical conformations in diverse oligopeptide sequences. In an approach to the de novo design of α,α motifs, the 16 residue peptides Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-Xxx-Pro-Val-Ala-Leu-Aib-Val-Ala-Leu-OMe (Xxx = D-Phe 1; Xxx = L-Phe 2) have been spectroscopically studied in solution. Analysis of nuclear Overhauser effects, delineation of solvent shielded NH groups and circular dichroism spectra establish helical conformations in both the peptides. Despite the presence of a potentially helix breaking, central, (D)Phe-(L)Pro segment, peptide 1 is forced into a continuous helical fold presumably as a consequence of the overriding stereochemical dominance of the Aib residues.