A β-amino acid modified heptapeptide containing a designed recognition element disrupts fibrillization of the amyloid β-peptide
A β-amino acid modified heptapeptide containing a designed recognition element disrupts fibrillization of the amyloid β-peptide
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DOI：
10.1002/psc.1271
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发表时间：
2010-09-01
影响因子：
2.1
通讯作者：
Castano, Eduardo M.
中科院分区：
文献类型：
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作者：
Castelletto, Valeria;Hamley, Ian W.;Castano, Eduardo M.
我们研究了先前由我们小组开发的肽β a β AKLVFF与a β(1-42)在水溶液中的复合物形成。利用圆二色光谱研究了β A β AKLVFF与A β(1-42)的相互作用，并研究了该物质在溶液中的二级结构。硫黄素T荧光光谱显示，与纯A β(1-42)溶液相比，β A β - AKLVFF/A β(1-42)混合物中的纤维数量更高。透射电镜和低温透射电镜显示，β - A β - AKLVFF与β(1-42)共孵育可形成延伸密集的支原纤维网络，这与单独A β(1-42)观察到的直原纤维非常不同。神经毒性试验表明，尽管β A β AKLVFF改变了A β(1-42)的纤化，但它并没有降低神经毒性，这表明在β A β AKLVFF/A β(1-42)混合物中仍然存在毒性低聚物A β(1-42)。我们的研究结果表明，我们设计的肽结合A β(1-42)并改变淀粉样蛋白原纤维的形态。事实证明，这并不一定会降低毒性。版权所有(c) 2010欧洲多肽协会和约翰威利父子有限公司。
We study the complex formation of a peptide beta A beta AKLVFF, previously developed by our group, with A beta(1-42) in aqueous solution. Circular dichroism spectroscopy is used to probe the interactions between beta A beta AKLVFF and A beta(1-42), and to study the secondary structure of the species in solution. Thioflavin T fluorescence spectroscopy shows that the population of fibers is higher in beta A beta AKLVFF/A beta(1-42) mixtures compared to pure A beta(1-42) solutions. TEM and cryo-TEM demonstrate that co-incubation of beta A beta AKLVFF with A beta(1-42) causes the formation of extended dense networks of branched fibrils, very different from the straight fibrils observed for A beta(1-42) alone. Neurotoxicity assays show that although beta A beta AKLVFF alters the fibrillization of A beta(1-42), it does not decrease the neurotoxicity, which suggests that toxic oligomeric A beta(1-42) species are still present in the beta A beta AKLVFF/A beta(1-42) mixtures. Our results show that our designed peptide binds to A beta(1-42) and changes the amyloid fibril morphology. This is shown to not necessarily translate into reduced toxicity. Copyright (c) 2010 European Peptide Society and John Wiley & Sons, Ltd.