Multiple ligand binding sites on Aβ(1-40) fibrils

Harry Levine

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Although the structures of Thioflavin T and another benzothiazole, BTA-1, are similar, they bind to Aβ non-competitively, probably to different sites on the Aβ (1-40) fibrils. The amyloid fibril-induced fluorescence of ThT that corresponds to a fraction of total ThT binding is not displaced by high concentrations of (S)-naproxen or (R)-ibuprofen, which are reported to potently block high affinity binding of the radiolabeled malononitrile FDDNP and derivatives. The binding of the benzothiazole ligands is significantly substoichiometric with respect to Aβ (1-40) monomer peptide, unlike Congo Red, which binds to Aβ (1-40) fibrils on a 1:1 basis with monomer peptide. These results indicate that there are multiple domains for ligand binding to amyloid fibrils and suggest that it may be possible to design ligands that bind selectively to particular forms of fibrils that are connected with the pathogenesis of Alzheimer's disease and potentially other protein misfolding diseases.

Original languageEnglish
Pages (from-to)5-14
Number of pages10
Issue number1
StatePublished - Mar 2005


  • BTA-1
  • Congo Red
  • Fluorescence
  • Ibuprofen
  • Naproxen
  • Non-competitive binding
  • Stoichiometry
  • Thioflavin T

ASJC Scopus subject areas

  • Internal Medicine


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