Modified EDTA selectively recognized Cu and its application in the disaggregation of β-amyloid-Cu (II)/Zn (II) aggregates.

The accumulation of the β-amyloid (Aβ) aggregates induced by Cu/Zn 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 Cu from Aβ-Cu (II) aggregates. The specific selectivity of EDTA-ASA towards Cu in Tris-HCl buffer solution was investigated by fluorescence measurements. It exhibits high recognition towards Cu with no significant interference of other competitive metal ions, which overcomes the deficiencies of EDTA. Importantly, the binding sites and binding mode for Cu 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 Cu chelating affinity was sufficient for EDTA-ASA to sequester Cu from Aβ-Cu (II) aggregates.