Multivalent interacting glycodendrimer to prevent amyloid-peptide fibril formation induced by Cu(II): A multidisciplinary approach
| Autor: | Gianvito Grasso, Anna Janaszewska, Monika Marcinkowska, Maria Francesca Ottaviani, Dietmar Appelhans, Marco Agostino Deriu, Barbara Klajnert-Maculewicz, Michela Cangiotti, Piotr Duchnowicz, Andrea Danani |
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| Rok vydání: | 2018 |
| Předmět: |
Circular dichroism
Amyloid glycodendrimers Peptide 02 engineering and technology Cu(II) 010402 general chemistry Fibril 01 natural sciences law.invention chemistry.chemical_compound law Dendrimer circular dichroism (CD) Organic chemistry General Materials Science Electrical and Electronic Engineering Electron paramagnetic resonance glycodendrimers amyloid peptide Cu(II) circular dichroism (CD) electron paramagnetic resonance (EPR) molecular modeling chemistry.chemical_classification molecular modeling Chemistry Fibrillogenesis 021001 nanoscience & nanotechnology Condensed Matter Physics Atomic and Molecular Physics and Optics 0104 chemical sciences amyloid peptide electron paramagnetic resonance (EPR) Biophysics Thioflavin 0210 nano-technology |
| Zdroj: | Nano Research. 11:1204-1226 |
| ISSN: | 1998-0000 1998-0124 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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