Amyloid probes based on Congo Red distinguish between fibrils comprising different peptides

Ted T. Ashburn, Hogyu Han, Brian F. McGuinness, Peter T. Lansbury

Research output: Contribution to journalArticle

65 Citations (Scopus)

Abstract

Background: Amyloid plaques, which characterize degenerating tissue in Alzheimer's disease (brain) and type Il diabetes (pancreas), were first visualized by staining with the dye Congo Red (CR). The ability of CR to recognize amyloid fibrils comprising diverse proteins suggests that the binding site includes an unidentified structural feature common to all amyloid fibrils. We set out to design and synthesize analogs of CR that could distinguish between fibrils comprising different peptides. Results: Relative affinities of several CR analogs for two model amyloid fibrils were measured and compared to that of CR. Amyloid fibrils comprising peptides based on the critical carboxyl terminus of the Alzheimer's disease amyloid protein β1-42 (β34-42) and the critical region of the type II diabetes pancreatic amyloid protein, IAPP (IAPP20-29) were tested. The ratio of affinities of each individual CR analog for the two amyloid fibrils varied considerably. Complexation of certain metal ions (Cu(II), Zn(II), Ni(II), Cd(II)) by a CR analog did not abolish its affinity for amyloid but changed the affinity ratio significantly. Conclusions: This study demonstrates that small organic and organometallic molecules are capable of detecting differences in amyloid fibril structure and/or amyloid protein sequence. Molecules of this type could have utility as neuropathological probes or imaging agents, since they are much easier to prepare and functionalize than antibodies and are specific for the fibrillar form of the amyloid proteins.

Original languageEnglish
Pages (from-to)351-358
Number of pages8
JournalChemistry and Biology
Volume3
Issue number5
DOIs
Publication statusPublished - 1996

Keywords

  • Alzheimer's disease
  • Amylin
  • Amyloid
  • Congo Red
  • Type II diabetes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

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