Abstract
Oligopeptide‐mediated helix stabilization of peptides in hydrophobic solutions was previously found by NMR and CD spectroscopic studies. The oligopeptide included the hydrophobic amino acids found in its parent peptide and were interposed by relevant basic or acidic amino acids. The strength of the interactions depended on the amino acid sequences. However, no helix‐stabilizing effect was seen for the peptides in phosphate buffer solution, because the peptides assumed a random‐coil structure. In order to ascertain whether the helix‐stabilizing effect of an oligopeptide on its parent peptide could operate in aqueous solution, model peptides EK17 (Ac‐AEAAAAEAAAKAAAAKA‐NH~2~) and IFM17 (Ac‐AEAAAAEIFMKAAAAKA‐NH~2~) that may assume an α‐helix in aqueous solutions were synthesized. Interactions were examined between various oligopeptides (EAAAK, KAAAE, EIFMK, KIFME, KIFMK and EYYEE) and EK17 or IFM17 in phosphate buffer and in 80% trifluoroethanol (TFE)–20% H~2~O solutions by CD spectra. EAAAK had little effect on the secondary structures of EK17 in both buffer and TFE solutions, while KAAAE, which has the reverse amino acid sequence of EAAAK, had a marked helix‐destabilizing effect on EK17 in TFE. EIFMK and KIFME were found to stabilize the α‐helical structure of EK17 in phosphate buffer solutions, whereas KIFMK and EYYEE destabilized the α‐helical structure of EK17. EIFMK and KIFME had no effect on IFM17, because unexpectedly, IFM17 had appreciable amounts of β‐sheet structure in buffer solution. It was concluded that in order for the helix‐stabilizing effects to operate effectively, the following factors should be satisfied: (1) the model peptide, the α‐helical conformation of which is to be stabilized, should essentially assume an α‐helical structure by nature, and (2) the hydrophobicity of the side‐chains of the oligopeptide should be high enough for the oligopeptide to perform stable specific side chain–side chain intermolecular hydrophobic interactions with the model peptide. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.