Design of Novel Helical Backbone. Conformational Energy Calculation and Synthesis of Sequential Polypeptide Containing Z-Dehydrophenylalanine and Proline Residues

Abstract

Theoretical conformational analysis was carried out on periodic polypeptides containing Z-dehydrophenylalanine (ΔZPhe) and Pro residues, poly(X-ΔZPhe-Pro) (X=Ala, Leu, D-Ala, and aminoisobutyric acid (Aib)), using the procedure of conformational energy minimization. The lowest-energy conformations were found to be a right-handed β11.9-helix for X=Ala, and a right-handed β5.1-helix for X=Gly. For X=Leu, D-Ala, and Aib, the lowest-energy conformation was found to be a left-handed β6.1–6.2-helix: the nearest phenyl-phenyl pairs took a center-to-center distance of 6.6–6.8 A and an edge-to-edge orientation. On the whole, phenyl groups were arranged in C2-type symmetry on the helical wheel. Poly(Leu-ΔZPhe-Pro) was synthesized by polymerizing the corresponding tripeptide with diphenylphosphoryl azide. The polypeptide in chloroform and in tetrahydrofuran showed a positive CD signal around 280 nm, which is ascribed to the absorption band of ΔZPhe residue. This CD pattern means that the screw angle between neighboring ΔZPhe transition moments is around 0° or 180°, suggesting the β6-helical conformation predicted above.