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Carboxymethylated-k-casein: A convenient tool for the identification of polyphenolic inhibitors of amyloid fibril formation

Journal Article


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Abstract


  • 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.

Authors


  •   Carver, John A. (external author)
  •   Duggan, Peter J. (external author)
  •   Ecroyd, Heath
  •   Liu, Yanqin (external author)
  •   Meyer, Adam G. (external author)
  •   Tranberg, C E. (external author)

Publication Date


  • 2010

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.

Scopus Eid


  • 2-s2.0-72049085497

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1988&context=scipapers

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/949

Has Global Citation Frequency


Number Of Pages


  • 6

Start Page


  • 222

End Page


  • 228

Volume


  • 18

Issue


  • 1

Abstract


  • 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.

Authors


  •   Carver, John A. (external author)
  •   Duggan, Peter J. (external author)
  •   Ecroyd, Heath
  •   Liu, Yanqin (external author)
  •   Meyer, Adam G. (external author)
  •   Tranberg, C E. (external author)

Publication Date


  • 2010

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.

Scopus Eid


  • 2-s2.0-72049085497

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1988&context=scipapers

Ro Metadata Url


  • http://ro.uow.edu.au/scipapers/949

Has Global Citation Frequency


Number Of Pages


  • 6

Start Page


  • 222

End Page


  • 228

Volume


  • 18

Issue


  • 1