Effect of amphipathic peptides with different α-helical contents on liposome-fusion

Abstract

The peptide-induced fusion of neutral and acidic liposomes was studied in relation to the amphiphilicities evaluated by α-helical contents of peptides by means of a car☐yfluorescein leakage assay, light scattering, a membrane intermixing assay and electron microscopy. An amphipathic mother peptide, Ac-(Leu-Ala-Arg-Leu) 3-NHCH 3 (4 3), and its derivatives, [Pro 6]4 3 (1), [Pro 2,6]4 3 (2), and [Pro 2,6,10]4 3 (3), which have very similar hydrophobic moments, caused a leakage of contents from small unilamellar vesicles composed of egg yolk phosphatidylcholine and egg yolk phosphatidic acid (3:1). The abilities of the peptides to induce the fusion of the acidic liposomes increased with increasing α-helical content: in acidic liposomes the helical contents were in the order of 4 3 1 2 3 (Lee et al. (1989) Chem. Lett., 599–602). Electron microscopic data showed that 1 caused a transformation of the small unilamellar vesicles (20–50 nm in diameter) to large ones (100–300 nm). Based on the fact that these peptides have very similar hydrophobic moments despite of decreasing in the mean residue hydrophobicities to some extent, it was concluded that the abilities of the peptides to induce the fusion of liposomes depend on the extent of amphiphilic conformation evaluated by α-helical contents of the peptides in the presence of liposomes. For neutral liposomes of egg yolk phosphatidylcholine, all the proline-containing peptides showed no fusogenic ability but weak leakage abilities, suggesting that the charge interaction between the basic peptides and acidic phospholipid is an important factor to induce the perturbation and fusion of the bilayer.