posted on 2024-11-14, 15:13authored byJohn A Carver, Peter J Duggan, Heath EcroydHeath Ecroyd, Yanqin Liu, Adam G Meyer, C E Tranberg
Reduced and carboxymethylated-κ-casein (RCM-κ-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 (Aβ), which is associated with Alzheimer’s disease. In this study, a series of flavonoids, many known to be inhibitors of Aβ fibril formation, were screened for their ability to inhibit RCM-κ-CN fibrilisation, and the results were compared with literature data on Aβ inhibition. Flavonoids that had a high degree of hydroxylation and molecular planarity gave good inhibition of RCM-κ-CN fibril formation. IC50 values were between 10- and 200-fold higher with RCM-κ-CN than literature results for Aβ fibril inhibition, however, with few exceptions, they showed a similar trend in potency. The convenience and reproducibility of the RCM-κ-CN assay make it an economic alternative first screen for Aβ inhibitory activity, especially for use with large compound libraries.
History
Citation
Carver, J. A., Duggan, P. J., Ecroyd, H., Liu, Y., Meyer, A. G. & Tranberg, C. E. (2010). Carboxymethylated-k-casein: A convenient tool for the identification of polyphenolic inhibitors of amyloid fibril formation. Bioorganic & Medicinal Chemistry: the tetrahedron journal for research at the interface of chemistry and biology, 18 (1), 222-228.