Potential amyloid plaque-specific peptides for the diagnosis of Alzheimer's disease.
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.
Larbanoix
Lionel
L
Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons-Hainaut, 24 Avenue du Champ de Mars, B-7000 Mons, Belgium.
Burtea
Carmen
C
Laurent
Sophie
S
Van Leuven
Fred
F
Toubeau
Gérard
G
Vander Elst
Luce
L
Muller
Robert N
RN
D000544:Alzheimer Disease / Q000175:diagnosis*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000473:pathology*; D003287:Contrast Media / Q000737:chemistry; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry; D019151:Peptide Library; D058225:Plaque, Amyloid / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar
D003287:Contrast Media; D010446:Peptide Fragments; D019151:Peptide Library