Per-6-substituted β-cyclodextrin libraries inhibit formation of β-amyloid-peptide (Aβ)-derived, soluble oligomers

Jiaxin Yu, Lara Bakhos, Lei Chang, Mark J. Holterman, William L. Klein, Duane L. Venton*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


Alzheimer's disease is the most common cause of dementia in older individuals with compelling evidence favoring neuron dysfunction and death triggered by assembled forms of Aβ1-42. While large neurotoxic amyloid fibrils have been known for years, recent studies show that soluble protofibril and Aβ1-42-derived diffusible ligands (ADDLs) may also be involved in neurotoxicity. In the present work, dot-blot immunoassays discriminating ADDLs from monomers were used to screen libraries of per-substituted β-cyclodextrin (β-CD) derivatives for inhibition of ADDLs formation. Libraries were prepared from per-6-iodo-β-CD by treatment with various amine nucleophiles. The most active library tested (containing >2000 derivatives) was derived from imidazole, N, N-dimethylethylenediamine and furfurylamine, which at 10 μM total library, inhibited ADDLs formation (10 nM Aβ1-42) over a period of 4 hours. The latter was confirmed by a western blot assay showing decreased amounts of the initially formed Aβ1-42 tetramer. These preliminary experiments suggest that derivatized forms of β-CD can interfere with the oligomerization process of Aβ1-42.

Original languageEnglish (US)
Pages (from-to)51-55
Number of pages5
JournalJournal of Molecular Neuroscience
Issue number1-2
StatePublished - Jan 1 2002


  • ADDLs
  • Alzheimer's
  • Beta amyloid
  • Beta cyclodextrin
  • Combinatorial chemistry

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


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