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https://hdl.handle.net/2440/61863
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Type: | Journal article |
Title: | Carboxymethylated-κ-casein: A convenient tool for the identification of polyphenolic inhibitors of amyloid fibril formation |
Other Titles: | Carboxymethylated-kappa-casein: A convenient tool for the identification of polyphenolic inhibitors of amyloid fibril formation |
Author: | Carver, J. Duggan, P. Ecroyd, H. Liu, Y. Meyer, A. Tranberg, C. |
Citation: | Bioorganic and Medicinal Chemistry, 2010; 18(1):222-228 |
Publisher: | Pergamon-Elsevier Science Ltd |
Issue Date: | 2010 |
ISSN: | 0968-0896 1464-3391 |
Statement of Responsibility: | John A. Carver, Peter J. Duggan, Heath Ecroyd, Yanqin Liu, Adam G. Meyer, C. Elisabet Tranberg |
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. |
Keywords: | Amyloid fibril κ-Casein Polyphenol Flavonoid Catechin Flavonol Isoflavone |
Rights: | Crown copyright © 2009 Published by Elsevier Ltd. |
DOI: | 10.1016/j.bmc.2009.10.063 |
Published version: | http://dx.doi.org/10.1016/j.bmc.2009.10.063 |
Appears in Collections: | Aurora harvest Chemistry and Physics publications IPAS publications |
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