Characterizing bathocuproine self-association and subsequent binding to Alzheimer's disease amyloid β-peptide by NMR

✍ Scribed by Shenggen Yao; Robert A Cherny; Ashley I. Bush; Colin L. Masters; Kevin J. Barnham

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 143 KB
• Volume: 10
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.539

✦ Synopsis

Abstract

Aggregated amyloid β‐peptide (Aβ) is the primary constituent of the extracellular plaques and perivascular amyloid deposits associated with Alzheimer's disease (AD). Deposition of the cerebral amyloid plaques is thought to be central to the disease progression. One such molecule that has previously been shown to ‘dissolve’ deposited amyloid in post‐mortem brain tissue is bathocuproine (BC). In this paper ^1^H NMR chemical shift analysis and pulsed field gradient NMR diffusion measurements were used to study BC self‐association and subsequent binding to Aβ. The results show that BC undergoes self‐association as its concentration increases. The association constant of BC dimerization, K~a~, was estimated to be 0.64 mM^−1^ at 25°C from ^1^H chemical shift analysis. It was also found that dimerization of BC appeared to be essential for its binding to Aβ. From the self‐association constant of BC, K~a~, the fraction of dimeric BC in the complex was obtained and the dissociation constant, K~d~, of BC bound to Aβ40 peptide was then determined to be ∼1 mM. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.