title: Carboxymethylated-kappa-casein: a convenient tool for the identification of polyphenolic inhibitors of amyloid fibril formation.
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.
authors.affiliation: School of Chemistry and Physics, The University of Adelaide, Adelaide, South Australia 5005, Australia.
authors.forename: John A
authors.initials: JA
authors.lastname: Carver
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Duggan
authors.forename: Heath
authors.initials: H
authors.lastname: Ecroyd
authors.forename: Yanqin
authors.initials: Y
authors.lastname: Liu
authors.forename: Adam G
authors.initials: AG
authors.lastname: Meyer
authors.forename: C Elisabet
authors.initials: CE
authors.lastname: Tranberg
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000682:Amyloid / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D002364:Caseins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008745:Methylation; D008892:Milk / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D002364:Caseins; D005419:Flavonoids