Department of Chemistry, University of Isfahan, Isfahan, Iran.
Department of Clinical Biochemistry School of Pharmacy and Pharmaceutical Sciences, and Bioinformatics Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
J Pept Sci. 2020 Feb;26(2):e3227. doi: 10.1002/psc.3227. Epub 2019 Dec 16.
The aggregation of Aβ peptide into amyloid fibrils in the brain is associated with Alzheimer's disease (AD). Inhibition of Aβ aggregation seemed a potential treatment for AD. It was previously shown that a short fragment of Aβ peptide (KLVFF, 16-20) bound Aβ inhibited its aggregation. In this work, using KLVFF peptide, we synthesized two peptide families and then evaluated their inhibitory capacities by conventional assays such as thioflavin T (ThT) fluorescence spectroscopy, turbidity measurement, and the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS). The effect of peptide terminal groups on its inhibitory activity was first studied. Subsequently, the influence of halogenated amino acids on peptide anti-aggregation properties was investigated. We found that iodinated peptide with amine in the N and amide in the C termini, respectively, was the best inhibitor of Aβ fibers formation. Halogenated peptides seemed to decrease the number of Aβ fibrils; however, they did not reduce Aβ cytotoxicity. The data obtained in this work seemed promising in developing potential peptide drugs for treatment of AD.
β淀粉样肽（Aβ）在脑内聚集形成纤维状沉淀与阿尔茨海默病（AD）密切相关。抑制 Aβ聚集似乎是 AD 的一种潜在治疗方法。先前的研究表明，Aβ 肽的一个短片段（KLVFF，16-20）可以结合 Aβ 并抑制其聚集。在这项工作中，我们使用 KLVFF 肽合成了两个肽家族，并通过常规方法（如硫黄素 T（ThT）荧光光谱法、浊度测量法和 3-(4,5-二甲基噻唑-2-基）-5-(3-羧基甲氧基苯基)-2-(4-磺基苯基)-2H-四唑（MTS））评估了它们的抑制能力。首先研究了肽末端基团对其抑制活性的影响。随后，研究了卤代氨基酸对肽抗聚集性质的影响。我们发现，N 端带有胺基、C 端带有酰胺基的碘化肽是 Aβ 纤维形成的最佳抑制剂。卤代肽似乎可以减少 Aβ 纤维的数量，但不会降低 Aβ 的细胞毒性。这项工作获得的数据为开发治疗 AD 的潜在肽类药物提供了有希望的依据。
