Characterizing bathocuproine self-association and subsequent binding to Alzheimer's disease amyloid beta-peptide by NMR.
Aggregated amyloid beta-peptide (A beta) 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 1H NMR chemical shift analysis and pulsed field gradient NMR diffusion measurements were used to study BC self-association and subsequent binding to A beta. The results show that BC undergoes self-association as its concentration increases. The association constant of BC dimerization, Ka, was estimated to be 0.64 mM(-1) at 25 degrees C from 1H chemical shift analysis. It was also found that dimerization of BC appeared to be essential for its binding to A beta. From the self-association constant of BC, Ka, the fraction of dimeric BC in the complex was obtained and the dissociation constant, Kd, of BC bound to A beta40 peptide was then determined to be approximately 1 mM.
Yao
Shenggen
S
The Walter and Eliza Hall Institute of Medical Research, and The Cooperative Research Center for Cellular Growth Factors, 1G Royal Parade, Parkville, VIC 3050, Australia.
Cherny
Robert A
RA
Bush
Ashley I
AI
Masters
Colin L
CL
Barnham
Kevin J
KJ
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006859:Hydrogen / Q000378:metabolism; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D010618:Phenanthrolines / Q000737:chemistry / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010618:Phenanthrolines; C078592:amyloid beta-protein (1-40); D006859:Hydrogen; C002478:bathocuproine