Concomitant occurrence of peptide 3(10)- and alpha-helices probed by NMR

Oligopeptides based on protein (Cα-trisubstituted) α-amino acids are known to undergo α-helix to unordered conformation transitions under appropriate experimental conditions. On the other hand, oligopeptides rich in Cα-tetrasubstituted α-amino acids present a rather peculiar stereochemistry due to significant constraints imposed on their conformational freedom by these residues. Specifically, most of the Cα-tetrasubstituted α-amino acids have been extensively documented to possess a very high intrinsic helix-forming capacity. The narrow conformational space accessible includes both the classical α-helix and the 310-helix. It was shown that among the Cα-tetrasubstituted chiral α-amino acids the β-branched Cα-methyl-L-valine [L-(αMe)Val] is the residue with the most pronounced bias toward the right-handed 310-helix. Strong initial experimental evidence has indicated that the terminally blocked −[L-(αMe)Val]8− sequence adopts a fully developed, right-handed 310-helical conformation both in the crystal state and in structure-supporting solvents. More recently, the interesting property of this peptide to fold in solution both in the 310- and in the α-helix has emerged. The type of helical conformation adopted was found to depend on experimental conditions, as clearly shown by vibrational and electronic CD techniques. Under appropriate conditions, the conformational transition from 310- to α-helix is very slow (the time scale is on the order of several days).