Selection of D-amino-acid peptides that bind to Alzheimer's disease amyloid peptide abeta1-42 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 Abeta(1-42). A randomized 12-mer peptide library presented on M13 phages was screened for peptides with binding affinity for the mirror image of Abeta(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 Abeta(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 Abeta 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 Abeta ligand in diagnosis and therapy of Alzheimer's disease are discussed.
Wiesehan
Katja
K
Forschungszentrum Jülich, IBI-2, 52425 Jülich, Germany.
Buder
Katrin
K
Linke
Reinhold P
RP
Patt
Stephan
S
Stoldt
Matthias
M
Unger
Eberhard
E
Schmitt
Bettina
B
Bucci
Enrico
E
Willbold
Dieter
D
D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000686:Amyloidosis / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019151:Peptide Library; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology
D016229:Amyloid beta-Peptides; D008024:Ligands; D010446:Peptide Fragments; D019151:Peptide Library; C078592:amyloid beta-protein (1-40)