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

Abstract

AbstractPivaloyl‐L‐Pro‐Aib‐N‐methylamide has been shown to possess one intramolecular hydrogen bond in (CD3)2SO solution, by 1H‐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 P21 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 ϕPro = −57.8°, ψPro = 139.3°, ϕAib = 61.4°, and ψAib = 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.