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Carboxymethylated-kappa-casein: a convenient tool for the identification of polyphenolic inhibitors of amyloid fibril formation.

Authors :
Carver JA
Duggan PJ
Ecroyd H
Liu Y
Meyer AG
Tranberg CE
Source :
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2010 Jan 01; Vol. 18 (1), pp. 222-8. Date of Electronic Publication: 2009 Nov 04.
Publication Year :
2010

Abstract

Reduced and carboxymethylated-kappa-casein (RCM-kappa-CN) is a milk-derived amyloidogenic protein that readily undergoes nucleation-dependent aggregation and amyloid fibril formation via a similar pathway to disease-specific amyloidogenic peptides like amyloid beta (Abeta), which is associated with Alzheimer's disease. In this study, a series of flavonoids, many known to be inhibitors of Abeta fibril formation, were screened for their ability to inhibit RCM-kappa-CN fibrilisation, and the results were compared with literature data on Abeta inhibition. Flavonoids that had a high degree of hydroxylation and molecular planarity gave good inhibition of RCM-kappa-CN fibril formation. IC(50) values were between 10- and 200-fold higher with RCM-kappa-CN than literature results for Abeta fibril inhibition, however, with few exceptions, they showed a similar trend in potency. The convenience and reproducibility of the RCM-kappa-CN assay make it an economic alternative first screen for Abeta inhibitory activity, especially for use with large compound libraries.<br /> (Crown Copyright (c) 2009. Published by Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1464-3391
Volume :
18
Issue :
1
Database :
MEDLINE
Journal :
Bioorganic & medicinal chemistry
Publication Type :
Academic Journal
Accession number :
19931462
Full Text :
https://doi.org/10.1016/j.bmc.2009.10.063