Type II β‐turn conformation of pivaloyl‐<scp>L</scp>‐prolyl‐α‐aminoisobutyryl‐<i>N</i>‐methylamide: Theoretical, spectroscopic, and X‐ray studies

Abstract

Abstract Pivaloyl‐ L ‐Pro‐Aib‐ N ‐methylamide has been shown to possess one intramolecular hydrogen bond in (CD 3 ) 2 SO solution, by 1 H‐nmr methods, suggesting the existence of β‐turns, with Pro‐Aib as the corner residues. Theoretical conformational analysis suggests that Type II β‐turn conformations are about 2 kcal mol −1 more stable than Type III structures. A crystallographic study has established the Type II β‐turn in the solid state. The molecule crystallizes in the space group P2 1 with a = 5.865 Å, b = 11.421 Å, c = 12.966 Å, β = 97.55°, and Z = 2. The structure has been refined to a final R value of 0.061. The Type II β‐turn conformation is stabilized by an intramolecular 4 → 1 hydrogen bond between the methylamide NH and the pivaloyl CO group. The conformational angles are ϕ Pro = −57.8°, ψ Pro = 139.3°, ϕ Aib = 61.4°, and ψ Aib = 25.1°. The Type II β‐turn conformation for Pro‐Aib in this peptide is compared with the Type III structures observed for the same segment in larger peptides.