期刊
JOURNAL OF PHYSICAL CHEMISTRY B
卷 118, 期 31, 页码 9298-9305出版社
AMER CHEMICAL SOC
DOI: 10.1021/jp503282m
关键词
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资金
- National Natural Science Foundation of China [21025313, 21003137, 21321063]
Dysfunctional interaction of amyloid-beta (A beta) with excess metal ions is proved to be related to the etiology of Alzheimer's disease (AD). Using metal-binding compounds to reverse metal-triggered A beta 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 beta(1-40) 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 beta(1-40) fibers is in the order of CQ > SDUC > EDTA. Therefore, the disaggregation ability of chelators to the A beta(1-40) fibers does not only depend on the binding affinity of the chelators with Cu2+. Strong self-assembly ability of SDUC and pi-pi interaction of the conjugate group of CQ also contributes toward the disaggregation of the Cu2+-triggered A beta(1-40) fibers and result in the formation of mixed small aggregates.
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