High affinity binding of monoclonal antibodies to the sequential epitope EFRH of beta-amyloid peptide is essential for modulation of fibrillar aggregation.
Monoclonal antibodies raised against the N-terminal of Alzheimer's beta-amyloid peptide (betaAP) were found to modulate its fibrillar aggregation. While mAbs 6C6 and 10D5 inhibit the formation of beta-amyloid fibrils, trigger disaggregation and reversal to its non-toxic form, mAb 2H3 is devoid of these properties. MAb 2H3 binds the sequence DAEFRHD, corresponding to position 1-7 of the betaAP with high affinity (2 x 10(-9) M) similar to its binding with the whole betaAP. The EFRH peptide strongly inhibits binding of mAbs 6C6 and 10D5 to betaAP, whereas it inhibits weakly the interaction of 2H3 with betaAP. Low affinity binding of mAb 2H3 to EFRH might explain its failure in prevention of beta-amyloid formation.
Frenkel
D
D
Department of Molecular Microbiology and Biotechnology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv, Israel.
Balass
M
M
Katchalski-Katzir
E
E
Solomon
B
B
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D001435:Bacteriophages; D001667:Binding, Competitive / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D015723:Gene Library; D006801:Humans; D008969:Molecular Sequence Data; D016874:Neurofibrillary Tangles / Q000276:immunology* / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D000939:Epitopes