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

Bioorganic & Medicinal Chemistry
John A CarverC 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.

References

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Citations

Nov 23, 2012·ACS Chemical Neuroscience·Laramie P JamesonSergei V Dzyuba
Dec 3, 2014·Biochemical and Biophysical Research Communications·Yanqin LiuTara L Pukala
Jan 26, 2016·Journal of Agricultural and Food Chemistry·Jihua LiuJohn A Carver
May 16, 2014·Molecular Neurobiology·Johant Lakey-BeitiaArmando A Durant
Aug 27, 2015·European Journal of Mass Spectrometry·Yanqin LiuTara L Pukala
May 4, 2011·Chembiochem : a European Journal of Chemical Biology·Alaina S DeTomaMi Hee Lim
Sep 28, 2012·Food & Function·Prashant BharadwajLouise Bennett
Jan 3, 2020·The Journal of Chemical Physics·Wei MaDražen Zanchi
Jul 1, 2019·Comprehensive Reviews in Food Science and Food Safety·Marlies A LambrechtJan A Delcour

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