Stereochemistry of \alpha-Aminoisobutyric Acid Peptides in Solution: Conformations of Decapeptides with a Central Triplet of Contiguous L-Amino Acids

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 $CD{Cl}_3$ and ${({CD}_3)}_2SO$ solutions by 270-MHz' H-nmr. In $CD{Cl}_3$ the presence of eight intramolecularly hydrogen-bonded NH groups has been established, consistent with a $3_{10}$-helical conformation, for both decapeptides. In ${({CD}_3)}_2SO$ only seven solvent-shielded NH groups are observed, supporting either an \alpha-helical conformation or a partially unfolded $3_{10}$-helix. Ir studies provided supporting evidence for intramolecularly hydrogen-bonded structures in $CH{Cl}_3$, 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 $3_{10}$-helical conformations in polar solvents like ${({CD}_3)}_2SO$.