Research Article

|

2018, 11(3): 1204–1226

|

https://doi.org/10.1007/s12274-017-1734-9

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

Anna Janaszewska1, Barbara Klajnert-Maculewicz1 (*), Monika Marcinkowska1, Piotr Duchnowicz2, Dietmar Appelhans3, Gianvito Grasso4, Marco A. Deriu4, Andrea Danani4 (*), Michela Cangiotti5, and Maria Francesca Ottaviani5,1 (*)

View Author's information

1 Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland
2 Department of Biophysics of Environmental Pollution, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland
3 Department Bioactive and Responsive Polymers, Leibniz Institute of Polymer Research, 01069 Dresden, Germany
4 SUPSI-DTI IDSIA- Dalle Molle Institute for Artificial Intelligence, CH-6928 Manno, Switzerland
5 Department of Pure and Applied Sciences, University of Urbino, 61029 Urbino, Italy

Keywords: glycodendrimers, amyloid peptide, Cu (II), circular dichroism (CD), electron paramagnetic resonance (EPR), molecular modeling
Full article PDF
Cite this article(Endnote)
Share this article
Metric

views: 148

Citations: 0

  • Abstract
  • References
  • Electronic Supplementary Material
ABSTRACT 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).
Related Article
Cite this article

Multivalent interacting glycodendrimer to prevent amyloid-peptide fibril formation induced by Cu(II): A multidisciplinary approach. Nano Res. 2018, 11(3): 1204–1226 https://doi.org/10.1007/s12274-017-1734-9

Download citation