The accumulation of the β-amyloid (Aβ) aggregates induced by Cu2+/Zn2+ in conjunction with toxicity is closely related to Alzheimer's disease (AD). Herein, we intended to improve the efficiency and selectivity of traditional chelator ethylenediaminetetraacetic acid (EDTA) combined with a fluorescent group 4-aminosalicylic acid (4-ASA)to acquire a novel potential chelator 4,4'-((2,2'-(ethane-1,2-diylbis((carboxymethyl)azanediyl))bis(acetyl))bis(azanediyl))bis(2-hydroxybenzoic acid) (EDTA-ASA) capable of disaggregating Aβ-Cu(II)/ Zn(II) aggregates. EDTA-ASA combines 4-ASA as fluorophore and multidentate amino nitrogen, hydroxyl and carboxyl groups to chelate Cu2+ from Aβ-Cu (II) aggregates. The specific selectivity of EDTA-ASA towards Cu2+ in Tris-HCl buffer solution was investigated by fluorescence measurements. It exhibits high recognition towards Cu2+ with no significant interference of other competitive metal ions, which overcomes the deficiencies of EDTA. Importantly, the binding sites and binding mode for Cu2+ were clarified through DFT calculations. The thioflavin-T (ThT) fluorescence analyses and transmission electron microscopy (TEM) results have revealed EDTA-ASA exhibited an enhanced disaggregation capability on Aβ-Cu (II)/Zn (II) aggregates in comparison to EDTA. The Cu2+ chelating affinity was sufficient for EDTA-ASA to sequester Cu2+ from Aβ-Cu (II) aggregates.

中文翻译：

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改性的EDTA选择性地识别Cu 2+及其在β-淀粉状Cu（II）/ Zn（II）聚集体的分解中的应用。

Cu2 + / Zn2 +诱导的β-淀粉样蛋白（Aβ）聚集体的积累与毒性密切相关，与阿尔茨海默氏病（AD）密切相关。在这里，我们旨在提高传统螯合剂乙二胺四乙酸（EDTA）与荧光基团4-氨基水杨酸（4-ASA）结合的效率和选择性，以获得一种新型的潜在螯合剂4,4'-（（（2,2'-能够分解Aβ-Cu（II）/ Zn（II）的（乙烷-1,2-二基双（（羧甲基）氮杂二基）双（乙酰基）双（氮杂二基）双（2-羟基苯甲酸）（EDTA-ASA） ）集合。EDTA-ASA结合了4-ASA作为荧光团和多齿氨基氮，羟基和羧基，以螯合Aβ-Cu（II）聚集体中的Cu2 +。通过荧光测量研究了EDTA-ASA对Tris-HCl缓冲溶液中Cu2 +的比选择性。它显示出对Cu2 +的高度认可，而没有其他竞争性金属离子的明显干扰，从而克服了EDTA的不足。重要的是，通过DFT计算明确了Cu2 +的结合位点和结合方式。硫黄素-T（ThT）荧光分析和透射电子显微镜（TEM）结果表明，与EDTA相比，EDTA-ASA在Aβ-Cu（II）/ Zn（II）聚集体上具有增强的分解能力。Cu2 +的螯合亲和力足以使EDTA-ASA从Aβ-Cu（II）聚集体中螯合Cu2 +。硫黄素-T（ThT）荧光分析和透射电子显微镜（TEM）结果表明，与EDTA相比，EDTA-ASA在Aβ-Cu（II）/ Zn（II）聚集体上具有增强的分解能力。Cu2 +的螯合亲和力足以使EDTA-ASA从Aβ-Cu（II）聚集体中螯合Cu2 +。硫黄素-T（ThT）荧光分析和透射电子显微镜（TEM）结果表明，与EDTA相比，EDTA-ASA在Aβ-Cu（II）/ Zn（II）聚集体上具有增强的分解能力。Cu2 +的螯合亲和力足以使EDTA-ASA从Aβ-Cu（II）聚集体中螯合Cu2 +。