Effect of amphipathic peptides with different alpha-helical contents on liposome-fusion.
The peptide-induced fusion of neutral and acidic liposomes was studied in relation to the amphiphilicities evaluated by alpha-helical contents of peptides by means of a carboxyfluorescein leakage assay, light scattering, a membrane intermixing assay and electron microscopy. An amphipathic mother peptide, Ac-(Leu-Ala-Arg-Leu)3-NHCH3 (4(3], and its derivatives, [Pro6]4(3) (1), [Pro2,6]4(3) (2), and [Pro2,6,10]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 alpha-helical content: in acidic liposomes the helical contents were in the order of 4(3) greater than 1 greater than 2 greater than 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 alpha-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.
Lee
S
S
Laboratory of Biochemistry, Faculty of Science, Kyushu University, Fukuoka, Japan.
Aoki
R
R
Oishi
O
O
Aoyagi
H
H
Yamasaki
N
N
D000595:Amino Acid Sequence; D005452:Fluoresceins / Q000737:chemistry; D008027:Light; D008081:Liposomes; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D010712:Phosphatidic Acids / Q000502:physiology; D010713:Phosphatidylcholines / Q000737:chemistry
D005452:Fluoresceins; D008081:Liposomes; D010455:Peptides; D010712:Phosphatidic Acids; D010713:Phosphatidylcholines; C024098:6-carboxyfluorescein