Conformational analysis of [D-Ala9]alpha-factor and [L-Ala9]alpha-factor in solution and in the presence of lipid

The conformations in solution and in the presence of lipid vesicles of [D-Ala9] and [L-Ala9] analogues of the alpha-factor (WHWLQLKPGQPMY) from the yeast Saccharomyces cerevisiae were examined by NMR spectroscopy. Although both peptides are flexible molecules, NOE and NH d delta/dT data indicate that the [D-Ala9]alpha-factor analogue in DMSO and aqueous solution adopts a type II beta-turn about residues 8 and 9. In contrast, various NMR parameters for the less active [L-Ala9] analogue do not provide evidence for a regular secondary structure in solution. Transfer NOE data indicate that for both peptides binding to the lipid is strongest for the N-terminal residues. The C-terminus of the [D-Ala9] analogue appears to be more constrained in the bound state than the C-terminus of the [L-Ala9] analogue. This result is consistent with transfer NOE evidence that the type II beta-turn conformation of the [D-Ala9]alpha-factor is maintained in the lipid bound state.