Nano Research

, Volume 11, Issue 3, pp 1204–1226 | Cite as

Multivalent interacting glycodendrimer to prevent amyloid-peptide fibril formation induced by Cu(II): A multidisciplinary approach

  • Anna Janaszewska
  • Barbara Klajnert-MaculewiczEmail author
  • Monika Marcinkowska
  • Piotr Duchnowicz
  • Dietmar Appelhans
  • Gianvito Grasso
  • Marco A. Deriu
  • Andrea DananiEmail author
  • Michela Cangiotti
  • Maria Francesca OttavianiEmail author
Research Article


Amyloid peptide fibrillogenesis induced by Cu(II) ions is a key event in the pathogenesis of Alzheimer’s disease. Dendrimers have been found to be active in preventing fibril formation. Therefore, they hold promise for the treatment of Alzheimer’s disease. In this study, the fibrillation mechanism of amyloid peptide Aβ 1-40 was studied by adding Cu(II) in the absence and presence of 4th generation poly(propyleneimine) glycodendrimer functionalized with sulfate groups, using dynamic light scattering (DLS), circular dichroism (CD), fluorescence, electron paramagnetic resonance (EPR) and molecular modeling (MD). The glycodendrimer was non-toxic to mHippoE-18 embryonic mouse hippocampal cells, selected as a nerve cell model, and decreased the toxicity of peptide aggregates formed after the addition of Cu(II). The binary systems of Cu(II)–glycodendrimer, Cu(II)–peptide, and glycodendrimer–peptide were first characterized. At the lowest Cu(II)/glycodendrimer molar ratios, Cu(II) was complexed by the internal-dendrimer nitrogen sites. After saturation of these sites, Cu(II) binding with sulfate groups occurred. Stable Cu(II)–peptide complexes formed within 5 min and were responsible for a transition from an α helix to a β-sheet conformation of Aβ 1-40. Glycodendrimer–peptide interactions provoked the stabilization of the α-helix, as demonstrated in the absence of Cu(II) by the Thioflavin T assay, and in the presence of Cu(II) by CD, EPR, and MD. Formation of fibrils is differentially modulated by glycodendrimer and Cu(II) concentrations for a fixed amount of Aβ 1-40. Therefore, this multidisciplinary study facilitated the recognition of optimal experimental conditions that allow the glycodendrimer to avoid the fibril formation induced by Cu(II).


glycodendrimers amyloid peptide Cu(II) circular dichroism (CD) electron paramagnetic resonance (EPR) molecular modeling 


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We wish to thank our students: Pawel Piatek and Agnieszka Karenko for their assistance with the collection of a part of the data. Authors also thank Mrs. Christiane Effenberg for synthesizing the glycodendirmer, Dr. Hartmut Komber for NMR measurements and Dr. Susanne Boye for AF4 measurements.

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Multivalent interacting glycodendrimer to prevent amyloid-peptide fibril formation induced by Cu(II): A multidisciplinary approach


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Copyright information

© Tsinghua University Press and Springer-Verlag GmbH Germany 2018

Authors and Affiliations

  • Anna Janaszewska
    • 1
  • Barbara Klajnert-Maculewicz
    • 1
    Email author
  • Monika Marcinkowska
    • 1
  • Piotr Duchnowicz
    • 2
  • Dietmar Appelhans
    • 3
  • Gianvito Grasso
    • 4
  • Marco A. Deriu
    • 4
  • Andrea Danani
    • 4
    Email author
  • Michela Cangiotti
    • 5
  • Maria Francesca Ottaviani
    • 5
    • 1
    Email author
  1. 1.Department of General Biophysics, Faculty of Biology and Environmental ProtectionUniversity of LodzLodzPoland
  2. 2.Department of Biophysics of Environmental Pollution, Faculty of Biology and Environmental ProtectionUniversity of LodzLodzPoland
  3. 3.Department Bioactive and Responsive PolymersLeibniz Institute of Polymer ResearchDresdenGermany
  4. 4.SUPSI-DTI IDSIA- Dalle Molle Institute for Artificial IntelligenceMannoSwitzerland
  5. 5.Department of Pure and Applied SciencesUniversity of UrbinoUrbinoItaly

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