Characterizing bathocuproine self-association and subsequent binding to Alzheimer's disease amyloid beta-peptide by NMR
- Author(s)
- Yao, SG; Cherny, RA; Bush, AI; Masters, CL; Barnham, KJ;
- Details
- Publication Year 2004-04,Volume 10,Issue #4,Page 210-217
- Journal Title
- JOURNAL OF PEPTIDE SCIENCE
- Publication Type
- Journal Article
- Abstract
- Aggregated amyloid beta-peptide (Abeta) 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 H-1 NMR chemical shift analysis and pulsed field gradient NMR diffusion measurements were used to study BC self-association and subsequent binding to Abeta. 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 25degreesC from H-1 chemical shift analysis. It was also found that dimerization of BC appeared to be essential for its binding to Abeta. From the self-association constant of BC, K-a, the fraction of dimetic BC in the complex was obtained and the dissociation constant, K-d, of BC bound to Abeta40 peptide was then determined to be similar to1mM. Copyright (C) 2003 European Peptide Society and John Wiley Sons, Ltd.
- Publisher
- JOHN WILEY & SONS LTD
- Keywords
- PANCREATIC TRYPSIN-INHIBITOR; FIELD-GRADIENT; A-BETA; DIFFUSION MEASUREMENTS; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; SENILE PLAQUES; ZINC; AGGREGATION; PROTEIN
- Publisher's Version
- https://doi.org/10.1002/psc.539
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2004-04-01 12:00:00