Stereochemistry of a-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-LeuAibAib-(L-Leu),-Aib-L-Leu-Aib-OMe have been studied in CDC1, and (CD,),SO solutions by 270-MHz' H-nmr. In CDCl,, the presence of eight intramolecularly hydrogen-bonded N H groups has been established, consistent with a 3,,,-helical conformation, for both decapeptides. In (CD,),SO, only seven solvent-shielded NH groups are observed, supporting either an a-helical conformation or a partially unfolded 3,0-helix. Ir studies provided supporting evidence for intramolecularly hydrogen-bonded structures in CHCI,, 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 3,0-helical conformations in polar solvents like (CD,),SO.