Kinetics of the interaction of amphipathic alpha-helical peptides with phosphatidylcholines.
The rate of association of three amphipathic alpha-helical peptides with phosphatidylcholine liposomes was examined to provide more detailed information on the relationship between peptide length and the kinetics of lipid interactions. When added to dimyristoylphosphatidylcholine (DMPC) or dipalmitoylphosphatidylcholine (DPPC) liposomes from a guanidine-HCl solution, a ten residue peptide rapidly decreased the turbidity of the liposomes. However, a related 17-residue peptide had only a minimal effect on liposome turbidity. A 14-residue peptide was intermediate in effectiveness. Similarly, when liposomes were added to peptides dissolved in an aqueous buffer, the ten residue peptide but not the 17-residue peptide cleared the turbid liposomes and the 14-residue peptide was intermediate in efficacy. The rate of binding to the liposomes was compared with the three peptides by measurements of the kinetics of energy transfer from the single tryptophan residue of the peptides to a fluorescent probe in the bilayer interior. The tryptophan residue of the ten residue peptide effectively transferred energy to the probe, while that of the 14-residue peptide was less effective. Little or no energy transfer was observed with the 17-residue peptide. The binding of the 10 residue peptide was rapid and complete within < 100 ms. The 14-residue peptide bound more slowly, but still within seconds. The time frames for binding are an order of magnitude shorter than those observed for lipid clearing. The relationship between peptide length, liposome clearing and lipid binding kinetics is discussed in terms of a possible competing peptide-peptide interaction in the aqueous phase and a slow rearrangement of the lipid bilayer.
McLean
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Marion Merrell Dow Research Institute, Cincinnati, OH 45215.
Hagaman
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D015060:1,2-Dipalmitoylphosphatidylcholine; D000595:Amino Acid Sequence; D004134:Dimyristoylphosphatidylcholine; D004735:Energy Transfer; D005456:Fluorescent Dyes; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D014364:Tryptophan
D005456:Fluorescent Dyes; D008051:Lipid Bilayers; D008081:Liposomes; D010455:Peptides; D010713:Phosphatidylcholines; D015060:1,2-Dipalmitoylphosphatidylcholine; D014364:Tryptophan; D004134:Dimyristoylphosphatidylcholine