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

AbstractThe 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 α‐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.