Department of Chemistry, Faculty of Sciences and Technology, University of Coimbra , 3004-535, Coimbra, Portugal.
Anal Chem. 2018 Feb 6;90(3):2285-2292. doi: 10.1021/acs.analchem.7b04686. Epub 2018 Jan 9.
The time-dependent structural modifications and oxidation behavior of specifically chosen five short amyloid beta (Aβ) peptides, Aβ, Aβ, Aβ, Aβ, and Aβ, fragments of the complete human Aβ peptide, were investigated by atomic force microscopy (AFM) and voltammetry. The objective was to determine the influence of different Aβ domains (VHHQ that contains electroactive histidine H residues, KLVFF that is the peptide hydrophobic aggregation core, and IIGLMVGGVV that is the C-terminus hydrophobic region), and of Aβ peptide hydrophobicity, in the fibrilization mechanism. The short Aβ peptides absence of aggregation or the time-dependent aggregation mechanisms, at room temperature, in free chloride media, within the time window from 0 to 48 h, were established by AFM via changes in their adsorption morphology, and by differential pulse voltammetry, via modifications of the amino acid residues oxidation peak currents. The first oxidation peak was of tyrosine Y residue and the second peak was of histidine H and methionine M residues oxidation. A correlation between the presence of an intact highly hydrophobic KLVFF aggregation core and the time-dependent changes on the Aβ peptides aggregation was found. The hydrophobic C-terminal domain IIGLMVGGVV, present in the Aβ peptide, also contributed to accelerate the formation of Aβ peptide aggregates and fibrils.
通过原子力显微镜（AFM）和伏安法研究了特定选择的五条短淀粉样蛋白β（Aβ）肽，即 Aβ、Aβ、Aβ、Aβ 和 Aβ 的结构随时间的变化和氧化行为，这些肽段是完整的人类 Aβ 肽的片段。目的是确定不同 Aβ 结构域（包含电化学活性组氨酸 H 残基的 VHHQ、肽疏水区聚集核心的 KLVFF 和 C 末端疏水区的 IIGLMVGGVV）以及 Aβ 肽疏水性对纤维化机制的影响。通过 AFM 观察其吸附形态的变化以及通过差分脉冲伏安法观察氨基酸残基氧化峰电流的变化，确定了短 Aβ 肽在室温下、在自由氯介质中、在 0 至 48 小时的时间窗口内不存在聚集或随时间变化的聚集机制。第一个氧化峰是酪氨酸 Y 残基的氧化峰，第二个氧化峰是组氨酸 H 和蛋氨酸 M 残基的氧化峰。发现存在完整的高度疏水性 KLVFF 聚集核心与 Aβ 肽聚集随时间的变化之间存在相关性。存在于 Aβ 肽中的疏水性 C 末端结构域 IIGLMVGGVV 也有助于加速 Aβ 肽聚集物和纤维的形成。
