title: Combined EPR and molecular modeling study of PPI dendrimers interacting with copper ions: effect of generation and maltose decoration.
abstract: Understanding the early onset of neurodegeneration is crucial to deploy specific treatments for patients before the process becomes irreversible. Copper has been proposed as a biomarker for many neurodegenerative disorders, being the ion released by pathologically unfolded proteins involved in many biochemical pathways. Dendrimers are macromolecules that bind metal ions with a large ion/ligand ratio, thus, allowing a massive collection of copper. This work provides structural information, obtained via molecular modeling and EPR, for the binding sites of copper in polypropyleneimine (PPI) dendrimers, especially in the maltose decorated form that has potential applications in diagnosis and therapies for various types of neurodegenerations. The analysis of the EPR spectra showed that, at the lowest Cu concentrations, the results are well supported by the calculations. Moreover, EPR analysis at increasing Cu(II) concentration allowed us to follow the saturation behavior of the interacting sites identified by the modeling study.
authors.affiliation: Department of Chemical and Pharmaceutical Sciences, University of Trieste , Via Giorgieri 1, I-34127 Trieste, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Furlan
authors.forename: Giovanni
authors.initials: G
authors.lastname: La Penna
authors.forename: Dietmar
authors.initials: D
authors.lastname: Appelhans
authors.forename: Michela
authors.initials: M
authors.lastname: Cangiotti
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Ottaviani
authors.forename: Andrea
authors.initials: A
authors.lastname: Danani
mesh_terms: D001665:Binding Sites; D003300:Copper / Q000737:chemistry*; D050091:Dendrimers / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D008320:Maltose / Q000737:chemistry*; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D011126:Polypropylenes / Q000737:chemistry*
chemical_list: D050091:Dendrimers; D011126:Polypropylenes; C443641:poly(propyleneimine); D008320:Maltose; D003300:Copper