Back to Search
Start Over
Carboxymethylated-kappa-casein: a convenient tool for the identification of polyphenolic inhibitors of amyloid fibril formation.
- 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.)
- Subjects :
- Alzheimer Disease metabolism
Amyloid beta-Peptides metabolism
Animals
Caseins antagonists & inhibitors
Caseins chemistry
Humans
Methylation
Milk chemistry
Structure-Activity Relationship
Amyloid antagonists & inhibitors
Amyloid metabolism
Caseins metabolism
Flavonoids chemistry
Flavonoids pharmacology
Subjects
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