par Larbanoix, Lionel 
;Burtea, Carmen;Laurent, Sophie ;Van Leuven, F.;Toubeau, Gérard ;Vander Elst, Luce;Muller, Robert
Référence Neurobiology of aging, 31, 10, page (1679-1689)
Publication Publié, 2010-10
;Burtea, Carmen;Laurent, Sophie ;Van Leuven, F.;Toubeau, Gérard ;Vander Elst, Luce;Muller, Robert Référence Neurobiology of aging, 31, 10, page (1679-1689)
Publication Publié, 2010-10
Article révisé par les pairs
| Résumé : | Amyloid plaques (AP) represent one of the main molecular hallmarks of Alzheimer's disease (AD). In order to develop new AP-specific contrast agents for AD molecular imaging, the phage display technology was used to identify peptides specific to amyloid-beta (A beta(42)). A random disulfide constrained heptapeptide phage display library was screened against A beta(42). After biopanning, 72 phage clones were isolated and their binding affinity to A beta(42) was evaluated by enzyme-linked immunosorbent assay (ELISA). The final library was enriched in two peptide sequences. The K(d) of candidate phage clones for binding to A beta(42) are in the picomolar range. The binding affinity for A beta(42) of two selected peptides was confirmed by ELISA, and the specific interaction with AP was validated by immunohistochemistry on brain sections. The preliminary MRI in vivo study, which was performed with a peptide functionalized contrast agent on AD transgenic mouse, showed encouraging results. To conclude, low molecular weight peptides presenting a specific affinity for A beta(42) were identified by phage display. As specific carriers, they have a real potential for molecular imaging of AD thanks to AP binding. |
