S. Castano et al., Ideally amphipathic beta-sheeted peptides at interfaces: structure, orientation, affinities for lipids and hemolytic activity of (KL)(m)K peptides, BBA-BIOMEMB, 1463(1), 2000, pp. 65-80
Designed to model ideally amphipathic beta-sheets, the minimalist linear (K
L)(m)K peptides (m = 4-7) were synthesized and proved to form stable films
at the air/water interface, they insert into compressed dimyristoylphosphat
idylcholine monolayers and interact with egg phosphatidylcholine vesicles.
Whatever the interface or the lateral pressure applied to the films. FT-IR
and polarization-modulated IRRAS spectroscopy developed in situ on the film
s indicated that all the peptides totally fold into intermolecular antipara
llel beta-sheets. Calculated spectra of the amide region allowed us to defi
ne the orientation of the beta-strands compared to the interface. It is con
cluded that such beta-sheets remain flat-oriented without deep perturbation
of zwitterionic phospholipids. Dansyl labelling at the N-terminus indicate
s that all the peptides are monomeric at a low concentration in aqueous buf
fer and bind to lipids with similar Dns burying. The affinities for zwitter
ionic lecithin mono- and bilayers, quantitatively estimated from buffer to
lipid partition constants, monotonically increased with peptide length, ind
icating that hydrophobicity is a limiting parameter for lipid and membrane
affinities. Peptides induced permeability increases on zwitterionic liposom
es, they are strongly hemolytic towards human erythrocytes and their activi
ty increases concurrently with length. Taking into account the lipid affini
ty, a hemolytic efficiency can be defined: at the same amount of peptide bo
und! this efficiency strongly increases with the peptide length. It is prop
osed that the first determinant step of membrane disturbance is the invasio
n of the outer membrane leaflet by these ideally amphipathic beta-sheeted s
tructures lying flat at the interface, like large rafts depending on the nu
mber of beta-strands. (C) 2000 Elsevier Science B.V. All rights reserved.