Copper and Zinc Mediated Oligomerisation of A[beta] Peptides

• Published in: International journal of peptide research and therapeutics 2006-06, Vol.12 (2), p.153
• Main Authors: Ali, Feda E, Separovic, Frances, Barrow, Colin J, Yao, Shenggen, Barnham, Kevin J
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Bacteria; Binding sites; Proteins
• ISSN: 1573-3149; 1573-3904
• DOI: 10.1007/s10989-006-9012-9

The accumulation of senile plaques composed primarily of aggregated amyloid β-peptide (Aβ), is the major characteristic of Alzheimer's disease. Many studies correlate plaque accumulation and the presence of metal ions, particularly copper and zinc. The metal binding sites of the amyloid Aβ peptide of Alzheimer's disease are located in the N-terminal region of the full-length peptide. In this work, the interactions with metals of a model peptide comprising the first 16 amino acid residues of the amyloid Aβ peptide, Aβ(1-16), were studied. The effect of Cu^sup 2+^ and Zn^sup 2+^binding to Aβ(1-16) on peptide structure and oligomerisation are reported. The results of ESI-MS, gel filtration chromatography and NMR spectroscopy demonstrated formation of oligomeric complexes of the peptide in the presence of the metal ions and revealed the stoichiometry of Cu^sup 2+^and Zn^sup 2+^ binding to Aβ(1-16), with Cu^sup 2+^showing a higher affinity for binding the peptide than Zn^sup 2+^.[PUBLICATION ABSTRACT]