Photophysical investigation of lipopeptides of myelin basic protein in phospholipid vesicles

We studied lipopeptide analogs of the human myelin basic protein, one of the putative autoantigens of multiple sclerosis disease, in the attempt to determine whether a lipid chain in myelin basic protein peptides may facilitate the insertion of the protein into the membrane bilayer. We used biomimetic models of the cellular membrane of lymphocytes; in particular, we examined how the presence of a lipid moiety in selected positions of the peptide sequence affects the incorporation of the peptide in vesicles of dipalmitoylphophatidylcho line. The resulting systems were characterized by means of UV-vis and fluorescence spectroscopy. The study of the solvatochromic properties of 7-amino-4-methylcoumarin-3-acetic acid provided information on the distribution of the peptides in the phospholipid vesicle and on the local dielectric properties experienced by the label. Further information on the mechanism of interaction of the lipopeptides with the phospholipid vesicles was obtained from fluorescence quenching experiments. The results showed the existence of different localization sites of the lipopeptide in the bilayer characterized by different accessibilities to the quencher. In the case of lipid-bound quenchers we obtained direct access to the position of the fluorescent label in the phospholipid vesicles for the various lipopeptides examined. These findings were interpreted in terms of molecular interactions and lipopeptide conformation and were correlated to clinical trials of the same substances.