High affinity binding of monoclonal antibodies to the sequential epitope EFRH of β-amyloid peptide is essential for modulation of fibrillar aggregation
High affinity binding of monoclonal antibodies to the sequential epitope EFRH of β-amyloid peptide is essential for modulation of fibrillar aggregation
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DOI：
10.1016/s0165-5728(99)00003-x
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发表时间：
1999-03-01
影响因子：
3.3
通讯作者：
Solomon, B
中科院分区：
文献类型：
--
作者：
Frenkel, D;Balass, M;Solomon, B
针对阿尔茨海默病 β-淀粉样肽 (β AP) N 端的单克隆抗体被发现可以调节其纤维聚集。 mAb 6C6 和 10D5 抑制 β-淀粉样蛋白原纤维的形成，引发解聚并逆转为无毒形式，而 mAb 2H3 则缺乏这些特性。 MAb 2H3 结合序列 DAEFRHD。对应于β AP的位置1-7，具有高亲和力(2 x 10(-9)M)，类似于其与整个β AP的结合。 EFRH 肽强烈抑制 mAb 6C6 和 10D5 与 β AP 的结合，而微弱抑制 2H3 与 β AP 的相互作用。 mAb 2H3 与 EFRH 的低亲和力结合可能解释了其未能预防 β-淀粉样蛋白形成的原因。 (C) 1999 Elsevier Science B.V. 保留所有权利。
Monoclonal antibodies raised against the N-terminal of Alzheimer's beta-amyloid peptide (beta AP) 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 beta AP with high affmity (2 x 10(-9)M) similar to its binding with the whole beta AP. The EFRH peptide strongly inhibits binding of mAbs 6C6 and 10D5 to beta AP, whereas it inhibits weakly the interaction of 2H3 with beta AP. Low affinity binding of mAb 2H3 to EFRH might explain its failure in prevention of beta-amyloid formation. (C) 1999 Elsevier Science B.V. All rights reserved.