Branched KLVFF tetramers strongly potentiate inhibition of β-amyloid aggregation

Sidhartha M. Chafekar, Hinke Malda, Maarten Merkx, E. W. Meijer, David Viertl, Hilal A. Lashuel, Frank Baas, Wiep Scheper

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The key pathogenic event in the onset of Alzheimer's disease (AD) is the aggregation of β-amyloid (Aβ) peptides into toxic aggregates. Molecules that interfere with this process might act as therapeutic agents for the treatment of AD. The amino acid residues 16-20 (KLVFF) are known to be essential for the aggregation of Aβ. In this study, we have used a first-generation dendrimer as a scaffold for the multivalent display of the KLVFF peptide. The effect of four KLVFF peptides attached to the dendrimer (K4) on Aβ aggregation was compared to the effect of monomeric KLVFF (K1). Our data show that K4 very effectively inhibits the aggregation of low-molecular-weight and protofibriliar Aβ1-42, into fibrils, in a concentration-dependent manner, and much more potently than K1. Moreover, we show that K4 can lead to the disassembly of existing aggregates. Our data lead us to propose that conjugates that bear multiple copies of KLVFF might be useful as therapeutic agents for the treatment of Alzheimer's disease.

Original languageEnglish
Pages (from-to)1857-1864
Number of pages8
Issue number15
Publication statusPublished - 15 Oct 2007



  • Aggregation inhibitors
  • Alzheimer's disease
  • Beta-amyloid peptides
  • Dendrimers
  • Multivalency
  • Neurochemistry

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

Cite this

Chafekar, S. M., Malda, H., Merkx, M., Meijer, E. W., Viertl, D., Lashuel, H. A., Baas, F., & Scheper, W. (2007). Branched KLVFF tetramers strongly potentiate inhibition of β-amyloid aggregation. ChemBioChem, 8(15), 1857-1864.