Type II \beta-Turn Conformation of Pivaloyl-L-Prolyl-\alpha-Aminoisobutyryl-N-Methylamide: Theoretical, Spectroscopic, and X-Ray Studies

Pivaloyl-L-Pro-Aib-N-methylamide has been shown to possess one intramolecular hydrogen bond in ${({CD}_3)}_2SO$ solution, by 'H-nmr methods, suggesting the existence of \beta-turns, with Pro-Aib as the corner residues. Theoretical conformational analysis suggests that Type II \beta-turn conformations are about 2 kcal $mol^{-1}$ more stable than Type III structures. A crystallographic study has established the Type II \beta-turn in the solid state. The molecule crystallizes in the space group ${P2}_1$ with a = 5.865 A, b = 11.421 A, c = 12.966 A, \beta = 97.55 deg, and Z = 2. The structure has been refined to a final R value of 0.061. The Type II \beta-turn conformation is stabilized by an intramolecular 4 \rightarrow 1 hydrogen bond between the methylamide NH and the pivaloyl CO group. The conformational angles are ${\phi}_{pro}$ = -57.8 deg, ${\psi}_{pro}$ = 139.3 deg, ${\phi}_{Aib}$ = 61.4 deg, and ${\psi}_{Aib}$ = 25.1 deg. The Type II \beta-turn conformation for Pro-Aib in this peptide is compared with the Type III structures observed for the same segment in larger peptides.