| Abstract
| - The amyloid beta (Aβ) peptide of Alzheimer’s disease binds copper(II), and the peptide-bound metal may be a source of reactive oxygen species and neurotoxicity. To circumvent peptide aggregation and reduce redox activity, there is growing interest in using metal chelates as drug therapeutics for AD, whose design requires accurate data on the affinity of Aβ peptides for copper(II). Reports on Cu2+ binding to Aβ range from ∼105 to ∼109; these valuesʼ being obtained for different peptide lengths (1−16, 1−28, 1−40, 1−42) at varying pH. Herein, we report that Cu2+ʼs binding to Aβ(1−40) at 37 °C occurs in a 1:1 stoichiometry with a pH-dependent binding constant: 1.1 (±0.2) × 109 M−1 and 2.4 (±0.2) × 109 M−1 at pH 7.2 and 7.4, respectively. Under identical conditions, Aβ(1−16) reveals a comparable binding constant, confirming that this portion of the peptide is the binding region. Several previously reported values can be reconciled with the current measurement by careful consideration of thermodynamics associated with the presence of competing ligands used to solubilize copper.
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