Inhibition of Alzheimer's amyloidosis by peptides that prevent beta-sheet conformation
Inhibition of Alzheimer's amyloidosis by peptides that prevent beta-sheet conformation
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DOI：
10.1006/bbrc.1996.1413
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发表时间：
1996-09-24
影响因子：
3.1
通讯作者：
Frangione, B
中科院分区：
文献类型：
--
作者：
Soto, C;Kindy, MS;Frangione, B
淀粉样蛋白β肽（A β）是阿尔茨海默病（AD）大脑中神经斑块的主要纤维成分，并与疾病的发病机制有关。我们假设淀粉样蛋白的形成可以被A β的同源肽（位置17-21）所抑制，这些肽具有相似的疏水性，但通过结合脯氨酸残基（抗β -sheet肽或β -sheet抑制剂）而采用β -sheet构象的倾向非常低。具有这些特征的11个残基肽与A β结合，抑制A β纤维的形成，并在体外部分分解已形成的原纤维。较短的抗β -片肽和含有d -氨基酸的类似物也能够抑制A - β纤维的形成。后者对蛋白水解降解更有抵抗力，可以作为设计更有效的肽衍生物来抑制体内淀粉样蛋白形成的起点。(C) 1996学术出版社，Inc.
Amyloid beta-peptide (A beta) is a major fibrillar component of neuritic plaques in Alzheimer's disease (AD) brains and is related to the pathogenesis of the disease. We hypothesized that amyloid formation could be inhibited by peptides homologous to A beta (position 17-21) with a similar degree of hydrophobicity, but with a very low propensity to adopt a beta-sheet conformation by incorporating proline residues (anti-beta-sheet peptides or beta-sheet inhibitors). An 11-residue peptide with these characteristics binds to A beta, inhibits A beta fibril formation and partially disaggregates preformed fibrils in vitro. Shorter anti-beta-sheet peptides and analogs containing D-amino acids are also able to inhibit A beta fibrillogenesis. The latter are more resistant to proteolytic degradation and may serve as a starting point to design more efficient peptides derivatives to inhibit amyloidogenesis in vivo. (C) 1996 Academic Press, Inc.