Stereochemistry of α-aminoisobutyric acid peptides in solution: conformations of decapeptides with a central triplet of contiguous L-amino acids

Abstract

The decapeptides Boc-Aib-L-Val-Aib-Aib-(L-Val)₃-Aib-L-Val-Aib-OMe and Boc-Aib-L-Leu-Aib-Aib-(L-Leu)₃-Aib-L-Leu-Aib-OMe have been studied in CDCl₃ and (CD₃)₂SO solutions by 270-MHz¹ H-nmr. In CDCl₃, the presence of eight intramolecularly hydrogen-bonded NH groups has been established, consistent with a 3₁₀-helical conformation, for both decapeptides. In (CD₃)₂SO, only seven solvent-shielded NH groups are observed, supporting either an -helical conformation or a partially unfolded 3₁₀-helix. Ir studies provided supporting evidence for intramolecularly hydrogen-bonded structures in CHCl₃, while CD studies suggest helical conformation in both decapeptides in various solvents. CD studies also support helical folding in the C-terminal hexapeptides. The central triplet of L-amino acids appears to destabilize 3₁₀-helical conformations in polar solvents like (CD₃)₂SO.