Katja Wiesehan1,2, Katrin Buder2, Reinhold P. Linke3, Stephan Patt4, Matthias Stoldt1,2,5, E. Unger2, Bettina Schmitt2, Enrico Bucci2,6, Dieter Willbold1,2,5
1Forschungszentrum Jülich IBI-2, 52425 Jülich, Germany, Fax: (+49) 2461-612023
2Institut für Molekulare Biotechnologie Beutenbergstrasse 11, 07745 Jena, Germany
3Max-Planck-Institut für Biochemie, Am Klopferspitz 18, 82152 Martinsried, Germany
4Friedrich-Schiller-Universität Institut für Neuropathologie, 07743 Jena, Germany
5Institut für Physikalische Biologie, Heinrich-Heine-Universität, 40225 Düsseldorf, Germany
6Istituto di Biostrutture e Bioimmagini Via Mezzocannone 6/8, 80134 Naples, Italy
Tóm tắt
AbstractA mirror image phage display approach was used to identify novel and highly specific ligands for Alzheimer's disease amyloid peptide Aβ(1–42). A randomized 12‐mer peptide library presented on M13 phages was screened for peptides with binding affinity for the mirror image of Aβ(1–42). After four rounds of selection and amplification the peptides were enriched with a dominating consensus sequence. The mirror image of the most representative peptide (D‐pep) was shown to bind Aβ(1–42) with a dissociation constant in the submicromolar range. Furthermore, in brain tissue sections derived from patients that suffered from Alzheimer's disease, amyloid plaques and leptomeningeal vessels containing Aβ amyloid were stained specifically with a fluorescence‐labeled derivative of D‐pep. Fibrillar deposits derived from other amyloidosis were not labeled by D‐pep. Possible applications of this novel and highly specific Aβ ligand in diagnosis and therapy of Alzheimer's disease are discussed.
