Reference : Enhanced Efficiency Of A Targeted Fusogenic Peptide
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Enhanced Efficiency Of A Targeted Fusogenic Peptide
Decout, A. [> > > >]
Labeur, C. [> > > >]
Goethals, M. [> > > >]
Brasseur, Robert mailto [Université de Liège - ULiège > > Gembloux Agro-Bio Tech >]
Vandekerckhove, J. [> > > >]
Rosseneu, M. [> > > >]
Biochimica et Biophysica Acta-Biomembranes
Yes (verified by ORBi)
[en] Membrane targeting was investigated as a potential strategy to increase the
fusogenic activity of an isolated fusion peptide. This was achieved by coupling
the fusogenic carboxy-terminal part of the beta-amyloid peptide (Abeta, amino
acids 29-40), involved in Alzheimer's disease, to a positively charged peptide
(PIP2-binding peptide, PBP) interacting specifically with a naturally occurring
negatively charged phospholipid, phosphatidylinositol 4, 5-bisphosphate (PIP2).
Peptide-induced vesicle fusion was spectroscopically evidenced by: (i) mixing of
membrane lipids, (ii) mixing of aqueous vesicular contents, and (iii) an
irreversible increase in vesicle size, at concentrations five to six times lower
than the Abeta(29-40) peptide. In contrast, at these concentrations the
PBP-Abeta(29-40) peptide did not display any significant activity on neutral
vesicles, indicating that negatively charged phospholipids included as targets in
the membranes, are required to compensate for the lower hydrophobicity of this
peptide. When the alpha-helical structure of the chimeric peptide was induced by
dissolving it in trifluoroethanol, an increase of the fusogenic potential of the
peptide was observed, supporting the hypothesis that the alpha-helical
conformation of the peptide is crucial to trigger the lipid-peptide interaction.
The specificity of the interaction between PIP2 and the PBP moiety, was shown by
the less efficient targeting of the chimeric peptide to membranes charged with
phosphatidylserine. These data thus demonstrate that the specific properties of
both the Abeta(29-40) and the PBP peptide are conserved in the chimeric peptide,
and that a synergetic effect is reached through chemical linkage of these two
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