Exploring interaction of beta-amyloid segment (25-35) with membrane models through paramagnetic probes.
The accumulation of beta-amyloid peptides into senile plaques is one of the hallmarks of Alzheimer's disease (AD). There is mounting evidence that the lipid matrix of neuronal cell membranes plays an important role in the beta-sheet oligomerization process of beta-amyloid. Abeta(25-35), the sequence of which is GSNKGAIIGLM, is a highly toxic segment of amyloid beta (Abeta)-peptides, which forms fibrillary aggregates. In the present work, two spin-labelled Abeta(25-35) analogues containing the nitroxide group of the amino acid TOAC (2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid) as a paramagnetic probe at the N- or the C-terminus of the peptide sequence, respectively, were synthesized in order to investigate the peptide-membrane interaction. The orientation and associated changes of the peptide conformation in the presence of different artificial membrane models (micelles, liposomes) were evaluated by electron paramagnetic resonance and circular dichroism techniques. The results of this study allowed us to propose a model in which the C-terminal portion of the peptide is highly associated to the membrane, while the N-terminal part extends into the aqueous phase with occasional contacts with the lipid head-group region. Interestingly, the interaction of the C-terminal portion of the peptide is particularly enhanced in the presence of sodium dodecyl sulfate (SDS) molecules.
Esposito
Cinzia
C
Dipartimento di Scienze Farmaceutiche, University of Salerno, 84084-Fisciano, Italy.
Tedeschi
Annamaria
A
Scrima
Mario
M
D'errico
Gerardino
G
Ottaviani
M Francesca
MF
Rovero
Paolo
P
D'ursi
Anna Maria
AM
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D002942:Circular Dichroism; D004347:Drug Interactions; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D008081:Liposomes / Q000737:chemistry; D008823:Micelles; D010446:Peptide Fragments / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D008081:Liposomes; D008823:Micelles; D010446:Peptide Fragments