N-terminal EFRH sequence of Alzheimer's beta-amyloid peptide represents the epitope of its anti-aggregating antibodies.
Monoclonal antibodies 6C6 and 10D5 raised against the N-terminal of beta-amyloid peptide interfere with the formation of beta-amyloid and trigger reversal to its non-toxic components. The epitopes of these antibodies were localized employing a library composed of filamentous phage displaying random combinatorial hexapeptides. Among 44 positive phage-clones, selected from the library by both antibodies, 40 clones carried the consensus sequence EFRH. These EFRH phage-clones bind specifically mAbs 6C6 or 10D5 with an apparent binding constant of approximately 10(-9) M. The peptide EFRH inhibits binding of mAbs 6C6 or 10D5 to beta-amyloid peptide in affinities identical to those obtained. with the peptides corresponding to positions 1-9, 1-16 and 1-40 of beta-peptide. These findings confirm that the peptide EFRH which is located at positions 3-6 within beta-amyloid peptide represents the sequential epitope of mAbs 6C6 and 10D5.
Department of Molecular Microbiology and Biotechnology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv, Israel.
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D
Frenkel
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M
Balass
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B
Solomon
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology*; D001435:Bacteriophages / Q000378:metabolism; D052160:Benzothiazoles; D001666:Binding Sites, Antibody / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005456:Fluorescent Dyes; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D052160:Benzothiazoles; D000939:Epitopes; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D013844:Thiazoles; C009462:thioflavin T