Department of Physical and Environmental Sciences, University of Toronto Scarborough, 1265 Military Trail, Toronto, ON, Canada.
Bioelectrochemistry. 2012 Apr;84:49-52. doi: 10.1016/j.bioelechem.2011.08.007. Epub 2011 Sep 13.
The development of generic inhibitors in order to control the formation of amyloid fibrils and early oligomers is still an unmet medical need. Here, we demonstrate the applicability of electrochemical analysis for the detection of β-sheet breaker peptide ligands that act as excellent inhibitors of Alzheimer's disease (AD) amyloid-β (Aβ) fibrils and oligomers in vitro. As the case study, a well-defined β-sheet breaker pentapeptide (LPFFD, FibIII) was utilized with Aβ(1-42) peptides. Square wave voltammetry (SWV) measurements were confirmed with simultaneous fluorescence analysis of the same incubated Aβ samples using a well-known fluorescent marker of β-sheet formation, Thioflavin T (ThT). Significant changes in the electrochemical signals were observed for the interaction of the Aβ oligomers with FibIII at the early stages of aggregation. The electrochemical approach, in principle, allowed monitoring β-sheet breaker-Aβ interactions on the time scale of aggregation in a label-free and cost-effective format using screen-printed carbon strip (SPCS) electrodes.
开发通用抑制剂以控制淀粉样纤维和早期寡聚体的形成仍然是未满足的医疗需求。在这里，我们展示了电化学分析在检测β-折叠破坏肽配体中的适用性，这些配体在体外作为阿尔茨海默病（AD）淀粉样β（Aβ）纤维和寡聚体的优异抑制剂。作为案例研究，使用了一种定义明确的β-折叠破坏五肽（LPFFD，FibIII）与 Aβ（1-42）肽。使用同步荧光分析相同孵育的 Aβ 样品证实了方波伏安法（SWV）测量，使用众所周知的β-折叠形成荧光标记物硫黄素 T（ThT）。在聚集的早期阶段，观察到 Aβ 寡聚体与 FibIII 相互作用时电化学信号发生了显著变化。该电化学方法原则上允许使用丝网印刷碳条（SPCS）电极以无标记和经济有效的格式在聚集的时间尺度上监测β-折叠破坏物-Aβ 相互作用。
