Basic amphipathic helical peptides induce destabilization and fusion of acidic and neutral liposomes.

We have studied the fusion of small unilamellar vesicles composed of egg PC and of a mixture of egg PC plus egg PA using various basic amphipathic peptides. Fusion was monitored by carboxyfluorescein leakage assay, light scattering, membrane intermixing assay, contents mixing assay and electron microscopy. Ac-(L-Leu-L-Ala-L-Arg-L-Leu)3-NHCH3 (peptide 4(3] and Ac-(L-Leu-L-Ala-L-Lys-L-Leu)3-NHCH3 (peptide 4'3), which have high hydrophobic moments, caused transformation of small unilamellar vesicles into larger and relatively homogeneous ones. Ac-(L-Leu-L-Leu-L-Ala-L-Arg-L-Leu)2-NHCH3 (5(2], which has medium hydrophobic moment, induced weak but appreciable fusion, while Ac-(L-Ala-L-Arg-L-Leu)3-NHCH3 (3(3] which has no helical structure did not show any fusion. However, peptides 4(3), 4'3 and 5(2) caused massive leakage of the contents from small unilamellar vesicles. These results indicated that interaction of the peptides with artificial membranes caused extensive perturbation of the lipid bilayer, followed by fusion. The fusogenic capacity of model basic peptides was correlated with the hydrophobic moment of each peptide when the peptides adopted an alpha-helical structure in the presence of acidic liposomes. Peptides 4(3) and 4'3 also showed weak fusogenic ability for neutral liposomes, while 5(2) and 3(3) showed no ability, suggesting that highly amphipathic peptides, such as 4(3), interact weakly but distinctly with neutral liposomes to fuse them.