Selection of D-amino-acid peptides that bind to Alzheimer's disease amyloid peptide Aβ1-42 by mirror image phage display(883 views) Wiesehan K, Buder K, Linke RP, Patt S, Stoldt M, Unger E, Schmitt B, Bucci E, Willbold D
Forschungszentrum Jülich, IBI-2, 52425 Jülich, Germany
Inst. fur Molekulare Biotechnologie, Beutenbergstrasse 11, 07745 Jena, Germany
Max-Planck-Institut fur Biochemie, Am Klopferspitz 18, 82152 Martinsried, Germany
Friedrich-Schiller-Universität, Institut für Neuropathologie, 07743 Jena, Germany
Institut fur Physikalische Biologie, Heinrich-Heine-Universität, 40225 Düsseldorf, Germany
Ist. di Biostrutture e Bioimmagini, Via Mezzoconnone 6/8, 80134 Naples, Italy
References: Not available.
Selection of D-amino-acid peptides that bind to Alzheimer's disease amyloid peptide Aβ1-42 by mirror image phage display
A 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.
Selection of D-amino-acid peptides that bind to Alzheimer's disease amyloid peptide Aβ1-42 by mirror image phage display