Department of Chemistry, The University of Reading, Reading RG6 6AD, UK.
J Pept Sci. 2010 Sep;16(9):443-50. doi: 10.1002/psc.1271.
We study the complex formation of a peptide betaAbetaAKLVFF, previously developed by our group, with Abeta(1-42) in aqueous solution. Circular dichroism spectroscopy is used to probe the interactions between betaAbetaAKLVFF and Abeta(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 betaAbetaAKLVFF/Abeta(1-42) mixtures compared to pure Abeta(1-42) solutions. TEM and cryo-TEM demonstrate that co-incubation of betaAbetaAKLVFF with Abeta(1-42) causes the formation of extended dense networks of branched fibrils, very different from the straight fibrils observed for Abeta(1-42) alone. Neurotoxicity assays show that although betaAbetaAKLVFF alters the fibrillization of Abeta(1-42), it does not decrease the neurotoxicity, which suggests that toxic oligomeric Abeta(1-42) species are still present in the betaAbetaAKLVFF/Abeta(1-42) mixtures. Our results show that our designed peptide binds to Abeta(1-42) and changes the amyloid fibril morphology. This is shown to not necessarily translate into reduced toxicity.
我们研究了先前由我们小组开发的肽 betaAbetaAKLVFF 与水溶液中的 Abeta(1-42)的复杂形成。圆二色性光谱用于探测 betaAbetaAKLVFF 与 Abeta(1-42) 之间的相互作用，并研究溶液中物种的二级结构。硫黄素 T 荧光光谱表明，与纯 Abeta(1-42)溶液相比，betaAbetaAKLVFF/Abeta(1-42)混合物中纤维的比例更高。TEM 和 cryo-TEM 表明，betaAbetaAKLVFF 与 Abeta(1-42) 共孵育会导致支化纤维的扩展密集网络的形成，与单独的 Abeta(1-42)观察到的直纤维非常不同。神经毒性测定表明，尽管 betaAbetaAKLVFF 改变了 Abeta(1-42)的纤维化，但它并没有降低神经毒性，这表明有毒的寡聚 Abeta(1-42)物种仍存在于 betaAbetaAKLVFF/Abeta(1-42)混合物中。我们的结果表明，我们设计的肽与 Abeta(1-42)结合并改变了淀粉样纤维形态。这并不一定转化为降低毒性。
