Journal of Molecular Neuroscience

, Volume 19, Issue 1–2, pp 51–55 | Cite as

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
Lead Compound Discovery And Optimization


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 nM1–42) 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.

Index Entries

Alzheimer’s beta amyloid ADDLs beta cyclodextrin combinatorial chemistry 


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Copyright information

© Humana Press Inc 2002

Authors and Affiliations

  • Jiaxin Yu
    • 1
  • Lara Bakhos
    • 3
  • Lei Chang
    • 3
  • Mark J. Holterman
    • 2
  • William L. Klein
    • 3
  • Duane L. Venton
    • 1
  1. 1.Department of Medicinal Chemistry and Pharmacognosy, College of PharmacyThe University of Illinois at ChicagoChicago
  2. 2.Department of Surgery, College of MedicineThe University of Illinois at ChicagoChicago
  3. 3.Department of Neurobiology and PhysiologyNorthwestern UniversityEvanston

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