The Effects of the Side Chains of Hydrophobic Aliphatic Amino Acid Residues in an Amphipathic Polypeptide on the Formation of α Helix and Its Association

The polypeptide α3, which was synthesized by us to produce an amphipathic helix structure, contains the regular three times repeated sequence (LETLAKA)3, and α3 forms a fibrous assembly. To clarify how the side chains of amino acid residues affect the formation of α helix, Leu residues, which are located in the hydrophobic surface of an amphipathic helix, were replaced by other hydrophobic aliphatic amino acid residues systematically, and the characters of the resulting polypeptides were studied. According to the circular dichroism (CD) spectra, the Ile-substituted polypeptides formed α helix like α3. However, their helix formation ability was weaker than that of α3 under some conditions. The Val-substituted polypeptides formed α helix only under restricted condition. The Ala-substituted polypeptides did not form α helix under any condition. Thus, it is clear that the order of the α helix formation ability is as follows: Leu ≥ Ile > Val > Ala. The formation of α helix was confirmed by Fourier Transform Infrared (FTIR) spectra. Through electron microscopic observation, it was clarified that the formation of the α helix structure correlates with the formation of a fibrous assembly. The amphipathic α helix structure would be stabilized by the formation of the fibrous assembly.