Quantification of the binding constant of copper(II) to the amyloid-beta peptide
| Autor: | Tessa M. Carducci, Lian Hong, John D. Simon, William D. Bush, Lanying Q. Hatcher |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Amyloid beta
chemistry.chemical_element Peptide Calorimetry Metal Materials Chemistry medicine Chelation Physical and Theoretical Chemistry chemistry.chemical_classification Reactive oxygen species Amyloid beta-Peptides biology Neurotoxicity Titrimetry medicine.disease Binding constant Copper Surfaces Coatings and Films chemistry Biochemistry visual_art visual_art.visual_art_medium biology.protein Biophysics Protein Binding |
| Zdroj: | The journal of physical chemistry. B. 112(27) |
| ISSN: | 1520-6106 |
| Popis: | The amyloid beta (A beta) 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 A beta peptides for copper(II). Reports on Cu2+ binding to A beta range from approximately 10(5) to approximately 10(9); these values' being obtained for different peptide lengths (1-16, 1-28, 1-40, 1-42) at varying pH. Herein, we report that Cu2+'s binding to A beta(1-40) at 37 degrees C occurs in a 1:1 stoichiometry with a pH-dependent binding constant: 1.1 (+/-0.2) x 10 (9) M (-1) and 2.4 (+/-0.2) x 10 (9) M(-1) at pH 7.2 and 7.4, respectively. Under identical conditions, A beta(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. |
| Databáze: | OpenAIRE |
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