Disaggregation Ability of Different Chelating Molecules on Copper Ion-Triggered Amyloid Fibers

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• 作者：Linyi Zhu ; Yuchun Han ; Chengqian He ; Xu Huang ; Yilin Wang
• 刊名：Journal of Physical Chemistry B
• 出版年：2014
• 出版时间：August 7, 2014
• 年：2014
• 卷：118
• 期：31
• 页码：9298-9305
• 全文大小：359K
• ISSN：1520-5207

文摘

Dysfunctional interaction of amyloid-尾 (A尾) with excess metal ions is proved to be related to the etiology of Alzheimer鈥檚 disease (AD). Using metal-binding compounds to reverse metal-triggered A尾 aggregation has become one of the potential therapies for AD. In this study, the ability of a carboxylic acid gemini surfactant (SDUC), a widely used metal chelator (EDTA), and an antifungal drug clioquinol (CQ) in reversing the Cu²⁺-triggered A尾(1鈥?0) fibers have been systematically studied by using turbidity essay, BCA essay, atomic force microscopy, transmission electron microscopy, and isothermal titration microcalorimetry. The results show that the binding affinity of Cu²⁺ with CQ, SDUC, and EDTA is in the order of CQ > EDTA > SDUC, while the disaggregation ability to Cu²⁺-triggered A尾(1鈥?0) fibers is in the order of CQ > SDUC > EDTA. Therefore, the disaggregation ability of chelators to the A尾(1鈥?0) fibers does not only depend on the binding affinity of the chelators with Cu²⁺. Strong self-assembly ability of SDUC and 蟺鈥撓€ interaction of the conjugate group of CQ also contributes toward the disaggregation of the Cu²⁺-triggered A尾(1鈥?0) fibers and result in the formation of mixed small aggregates.