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Diffusion and aggregation of Alzheimer's A beta(1-40) peptide in aqueous trifluoroethanol solutions as studied by pulsed field gradient NMR

机译:脉冲场梯度NMR研究阿尔茨海默氏病Aβ(1-40)肽在三氟乙醇水溶液中的扩散和聚集

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Pulsed field gradient nuclear magnetic resonance technique was applied to measure the self-diffusion coefficient of A beta(1-40) peptide in trifluoroethanol (TFE) and mixed solvent TFE-water (D2O) buffer (pD 7.8) at 293 K. The data were analyzed on the basis of the Stokes model and the hard-sphere approach was used to estimate self-diffusion coefficients. It was found that the extent of the A beta(1-40) aggregation in TFE solutions depends on the concentration of the peptide and the sample preparation protocol. After soft mixing, i.e., without any additional mechanical pretreatment of the peptide, the peptide is present in the monomeric form in TFE solutions. However, the additional water-bath sonication of the sample during the dissolution of A beta(1-40) in TFE enforces oligomerization of the peptide with the size of aggregates ranging from tetra- to hexamers. An increase of D2O in the mixed TFE-D2O solvent of up to 75% leads to the aggregation of the larger part of the peptide. However, the components of self-diffusion coefficients related to low-mass A beta(1-40). oligomers (dimers and trimers) were not observed in the diffusion decay curves. The most probable explanation is that dimers and trimers are not the principal intermediate species in the aggregation of A beta(1-40) peptide.
机译:应用脉冲场梯度核磁共振技术在293 K下测量A beta(1-40)肽在三氟乙醇(TFE)和混合溶剂TFE-水(D2O)缓冲液(pD 7.8)中的自扩散系数。数据在Stokes模型的基础上进行了分析,并使用硬球法估算了自扩散系数。发现在TFE溶液中A beta(1-40)聚集的程度取决于肽的浓度和样品制备方案。在软混合之后,即,在没有任何额外的肽的机械预处理的情况下,该肽以单体形式存在于TFE溶液中。但是,在TFE中溶解A beta(1-40)时,样品需要进行额外的水浴超声处理,从而使多肽发生寡聚,聚集体的大小从四聚体到六聚体不等。在混合的TFE-D2O溶剂中D2O的增加高达75%会导致大部分肽的聚集。但是,自扩散系数的成分与低质量A beta(1-40)有关。在扩散衰减曲线中未观察到低聚物(二聚体和三聚体)。最可能的解释是二聚体和三聚体不是A beta(1-40)肽聚集中的主要中间物种。

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