Advertisement

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

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).

Keywords

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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Notes

Acknowledgements

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.

Supplementary material

12274_2017_1734_MOESM1_ESM.pdf (1.6 mb)
Multivalent interacting glycodendrimer to prevent amyloid-peptide fibril formation induced by Cu(II): A multidisciplinary approach

References

  1. [1]
    Bertram, L.; Tanzi, R. E. The genetic epidemiology of neurodegenerative disease. J. Clin. Invest. 2005, 115, 1449–1457.CrossRefGoogle Scholar
  2. [2]
    Verma, M.; Vats, A.; Taneja, V. Toxic species in amyloid disorders: Oligomers or mature fibrils. Ann. Indian Acad. Neurol. 2015, 18, 138–145.CrossRefGoogle Scholar
  3. [3]
    Olesen, J.; Gustavsson, A.; Svensson, M.; Wittchen, H.-U.; Jönsson, B. The economic cost of brain disorders in Europe. Eur. J. Neurol. 2012, 19, 155–162.CrossRefGoogle Scholar
  4. [4]
    WHO. Dementia: Fact sheet N°362; World Health Organization: Geneva, 2015.Google Scholar
  5. [5]
    Seltzer, B.; Zolnouni, P.; Nunez, M.; Goldman, R.; Kumar, D.; Ieni, J.; Richardson, S. Donepezil "402" Study Group. Efficacy of donepezil in early-stage Alzheimer disease. A randomized placebo-controlled trial. Arch. Neurol. 2004, 61, 1852–1856.CrossRefGoogle Scholar
  6. [6]
    Yiannopoulou, K. G.; Papageorgiou, S. G. Current and future treatments for Alzheimer’s disease. Ther. Adv. Neurol. Disord. 2013, 6, 19–33.CrossRefGoogle Scholar
  7. [7]
    Colvin, V. L.; Kulinowski, K. M. Nanoparticles as catalysts for protein fibrillation. Proc. Natl. Acad. Sci. USA 2007, 104, 8679–8680.CrossRefGoogle Scholar
  8. [8]
    Parveen, R.; Shamsi, T. N.; Fatima, S. Nanoparticles–protein interaction: Role in protein aggregation and clinical implications. Int. J. Biol. Macromol. 2017, 94, 386–395.CrossRefGoogle Scholar
  9. [9]
    Cabaleiro-Lago, C.; Quinlan-Pluck, F.; Lynch, I.; Lindman, S.; Minogue, A. M.; Thulin, E.; Walsh, D. M.; Dawson, K. A.; Linse, S. Inhibition of amyloid β protein fibrillation by polymeric nanoparticles. J. Am. Chem. Soc. 2008, 130, 15437–15443.CrossRefGoogle Scholar
  10. [10]
    Ottaviani, M. F.; Mazzeo, R.; Cangiotti, M.; Fiorani, L.; Majoral, J. P.; Caminade, A. M.; Pedziwiatr, E.; Bryszewska, M.; Klajnert, B. Time evolution of the aggregation process of peptides involved in neurodegenerative diseases and preventing aggregation effect of phosphorus dendrimers studied by EPR. Biomacromolecules 2010, 11, 3014–3021.CrossRefGoogle Scholar
  11. [11]
    Appelhans, D.; Benseny, N.; Klementiveva, O.; Bryszewska, M.; Klajnert, B.; Cladera, J. Dendrimers as antiamyloidogenic agents. Dendrimer-amyloid aggregates morphology and cell toxicity. In Dendrimers in Biomedical Applications; Klajnert, B.; Peng, L.; Cena, V., Eds.; RSC Publishing: Cambridge, UK, 2013; pp 1–13.Google Scholar
  12. [12]
    Aulenta, F.; Hayes, W.; Rannard, S. Dendrimers: A new class of nanoscopic containers and delivery devices. Eur. Polym. J. 2003, 39, 1741–1771.CrossRefGoogle Scholar
  13. [13]
    Malik, N.; Wiwattanapatapee, R.; Klopsch, R.; Lorenz, K.; Frey, H.; Weener, J. W.; Meijer, E. W.; Paulus, W.; Duncan, R. Dendrimers: Relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo. J. Control. Release 2000, 65, 133–148.CrossRefGoogle Scholar
  14. [14]
    Barrett, T.; Ravizzini, G.; Choyke, P. L.; Kobayashi, H. Dendrimers in medical nanotechnology. IEEE Eng. Med. Biol. Mag. 2009, 28, 12–22.CrossRefGoogle Scholar
  15. [15]
    Bullen, H. A.; Hemmer, R.; Haskamp, A.; Cason, C.; Wall, S.; Spaulding, R.; Rossow, B.; Hester, M.; Caroway, M.; Haik K. L. Evaluation of biotinylated PAMAM dendrimer toxicity in models of the blood brain barrier: A biophysical and cellular approach. J. Biomater. Nanobiotechnol. 2011, 2, 485–493.CrossRefGoogle Scholar
  16. [16]
    Appelhans, D.; Klajnert-Maculewicz, B.; Janaszewska, A.; Lazniewska, J.; Voit, B. Dendritic glycopolymers based on dendritic polyamine scaffolds: View on their synthetic approaches, characteristics and potential for biomedical applications. Chem. Soc. Rev. 2015, 44, 3968–3996.CrossRefGoogle Scholar
  17. [17]
    Klajnert, B.; Cortijo-Arellano, M.; Cladera, J.; Bryszewska, M. Influence of dendrimer’s structure on its activity against amyloid fibril formation. Biochem. Biophys. Res. Commun. 2006, 345, 21–28.CrossRefGoogle Scholar
  18. [18]
    Klajnert, B.; Cortijo-Arellano, M.; Bryszewska, M.; Cladera, J. Influence of heparin and dendrimers on the aggregation of two amyloid peptides related to Alzheimer’s and prion diseases. Biochem. Biophys. Res. Commun. 2006, 339, 577–582.CrossRefGoogle Scholar
  19. [19]
    Klajnert, B.; Cortijo-Arellano, M.; Cladera, J.; Majoral, J. P.; Caminade, A.-M.; Bryszewska M. Influence of phosphorus dendrimers on the aggregation of the prion peptide PrP 185–208. Biochem. Biophys. Res. Commun. 2007, 364, 20–25.CrossRefGoogle Scholar
  20. [20]
    Klementieva, O.; Benseny-Cases, N.; Gella, A.; Appelhans, D.; Voit, B.; Cladera, J. Dense shell glycodendrimers as potential nontoxic anti-amyloidogenic agents in Alzheimer’s disease. Amyloid-dendrimer aggregates morphology and cell toxicity. Biomacromolecules 2011, 12, 3903–3909.CrossRefGoogle Scholar
  21. [21]
    Benseny-Cases, N.; Klementieva, O.; Cladera, J. Dendrimers antiamyloidogenic potential in neurodegenerative diseases. New J. Chem. 2012, 36, 211–216.CrossRefGoogle Scholar
  22. [22]
    Wasiak, T.; Ionov, M.; Nieznanski, K.; Nieznanska, H.; Klementieva, O.; Granell, M.; Cladera, J.; Majoral, J.-P.; Caminade, A.-M.; Klajnert, B. Phosphorus dendrimers affect Alzheimer’s (Aβ1–28) peptide and MAP-Tau protein aggregation. Mol. Pharm. 2012, 9, 458–469.CrossRefGoogle Scholar
  23. [23]
    McCarthy, J. M.; Moreno, B. R.; Filippini, D.; Komber, H.; Maly, M.; Cernescu, M.; Brutschy, B.; Appelhans, D.; Rogers, M. S. Influence of surface groups on poly(propylene imine) dendrimers antiprion activity. Biomacromolecules 2013, 14, 27–37.CrossRefGoogle Scholar
  24. [24]
    Milowska, K.; Malachowska, M.; Gabryelak, T. PAMAM G4 dendrimers affect the aggregation of α-synuclein. Int. J. Biol. Macromol. 2011, 48, 742–746.CrossRefGoogle Scholar
  25. [25]
    Milowska, K.; Gabryelak, T.; Bryszewska, M.; Caminade, A.-M.; Majoral, J.-P. Phosphorus-containing dendrimers against α-synuclein fibril formation. Int. J. Biol. Macromol. 2012, 50, 1138–1143.CrossRefGoogle Scholar
  26. [26]
    Milowska, K.; Grochowina, J.; Katir, N.; El Kadib, A.; Majoral, J.-P.; Bryszewska, M.; Gabryelak T. Interaction between viologen-phosphorus dendrimers and α-synuclein. J. Lumin. 2013, 134, 132–137.CrossRefGoogle Scholar
  27. [27]
    Milowska, K.; Grochowina, J.; Katir, N.; El Kadib, A.; Majoral, J.-P.; Bryszewska, M.; Gabryelak T. Viologen-phosphorus dendrimers inhibit α-synuclein fibrillation. Mol. Pharm. 2013, 10, 1131–1137.CrossRefGoogle Scholar
  28. [28]
    Zeliger, H. I.; Lipinski, B. Physiochemical basis of human degenerative disease. Interdiscip. Toxicol. 2015, 8, 15–21.CrossRefGoogle Scholar
  29. [29]
    Crichton, R. R.; Ward, R. J. Metal-Based Neurodegeneration: From Molecular Mechanisms to Therapeutic Strategies; John Wiley & Sons: Chichester, 2006.Google Scholar
  30. [30]
    Crichton, R. R.; Ward, R. J. Metal-Based Neurodegeneration: From Molecular Mechanisms to Therapeutic Strategies, 2nd ed.; John Wiley & Sons, Ltd.: Chichester, UK, 2014.Google Scholar
  31. [31]
    Gaggelli, E.; Kozlowski, H.; Valensin, D.; Valensin, G. Copper homeostasis and neurodegenerative disorders (Alzheimer’s, prion, and Parkinson’s diseases and amyotrophic lateral sclerosis). Chem. Rev. 2006, 106, 1995–2044.CrossRefGoogle Scholar
  32. [32]
    Kozlowski, H.; Janicka-Klos, A.; Brasun, J.; Gaggelli, E.; Valensin, D.; Valensin G. Copper, iron, and zinc ions homeostasis and their role in neurodegenerative disorders (metal uptake, transport, distribution and regulation). Coord. Chem. Rev. 2009, 253, 2665–2685.CrossRefGoogle Scholar
  33. [33]
    Faller, P.; Hureau, C.; La Penna, G. Metal ions and intrinsically disordered proteins and peptides: From Cu/Zn amyloid-β to general principles. Acc. Chem. Res. 2014, 47, 2252–2259.CrossRefGoogle Scholar
  34. [34]
    Karr, J. W.; Kaupp L. J.; Szalai V. A. Amyloid-β binds Cu2+ in a mononuclear metal ion binding site. J. Am. Chem. Soc. 2004, 126, 13534–13538.CrossRefGoogle Scholar
  35. [35]
    Liu, S. T.; Howlett, G.; Barrow, C. J. Histidine-13 is a crucial residue in the zinc ion-induced aggregation of the Aβ peptide of Alzheimer’s disease. Biochemistry 1999, 38, 9373–9378.CrossRefGoogle Scholar
  36. [36]
    La Penna, G.; Hureau, C.; Andreussi, O.; Faller, P. Identifying, by first-principles simulations, Cu[amyloid-β]_species making Fenton-type reactions in Alzheimer’s disease. J. Phys. Chem. B 2013, 117, 16455–16467.CrossRefGoogle Scholar
  37. [37]
    Kozłowski, H.; Luczkowski, M.; Valensin, D.; Valensin, G. Metal ion binding properties of proteins related to neurodegeneration. In Neurodegenerative Diseases and Metal Ions: Metal Ions in Life Science, vol. 1; Sigel, A.; Sigel, H.; Sigel, R. K. O., Eds.; John Wiley & Sons, Ltd.: Chichester, UK, 2006.Google Scholar
  38. [38]
    Vašák, M.; Meloni, G. Metallothionein-3, zinc, and copper in the central nervous system. In Metallothioneins and Related Chelators; Sigel, A.; Sigel, H.; Sigel, R. K. O., Eds.; The Royal Society of Chemistry: Cambridge, 2009; pp 319–352.Google Scholar
  39. [39]
    Klementieva, O.; Aso, E.; Filippini, D.; Benseny-Cases, N.; Carmona, M.; Juvés, S.; Appelhans, D.; Cladera, J.; Ferrer, I. Effect of poly(propylene imine) glycodendrimers on β-amyloid aggregation in vitro and in APP/PS1 transgenic mice, as a model of brain amyloid deposition and Alzheimer’s disease. Biomacromolecules 2013, 14, 3570–3580.CrossRefGoogle Scholar
  40. [40]
    Klajnert, B.; Appelhans, D.; Komber, H.; Morgner, N.; Schwarz, S.; Richter, S.; Brutschy, B.; Ionov, M.; Tonkikh, A. K.; Bryszewska, M. et al. The influence of densely organized maltose shells on the biological properties of poly(propylene imine) dendrimers: New effects dependent on Hydrogen bonding. Chem.-Eur. J. 2008, 14, 7030–7041.CrossRefGoogle Scholar
  41. [41]
    McCarthy, J. M.; Franke, M.; Resenberger, U. K.; Waldron, S.; Simpson, J. C.; Tatzelt, J.; Appelhans, D.; Rogers, M. S. Anti-prion drug mPPIg5 inhibits PrPC conversion to PrPSc. PLoS One 2013, 8, e55282.CrossRefGoogle Scholar
  42. [42]
    Furlan, S.; La Penna, G.; Appelhans, D.; Cangiotti, M.; Ottaviani, M. F.; Danani, A. Combined EPR and molecular modeling study of PPI dendrimers interacting with copper ions: Effect of generation and maltose decoration. J. Phys. Chem. B 2014, 118, 12098–12111.CrossRefGoogle Scholar
  43. [43]
    Ziemba, B.; Janaszewska, A; Ciepluch, K; Krotewicz, M.; Fogel, W. A.; Appelhans, D.; Voit, B.; Klajnert, B.; Bryszewska, M. In vivo toxicity of poly(propyleneimine) dendrimers. J. Biomed. Mater. Res. Part A 2011, 99, 261–268.CrossRefGoogle Scholar
  44. [44]
    Rossi, J. C.; Maret, B.; Vidot, K.; Francoia, J. P.; Cangiotti, M.; Lucchi, S.; Coppola, C.; Ottaviani, M. F. Multi-technique characterization of poly-L-lysine dendrigrafts-Cu(II) complexes for biocatalysis. Macromol. Biosci. 2015, 15, 275–290.CrossRefGoogle Scholar
  45. [45]
    Ottaviani, M. F.; El Brahmi, N.; Cangiotti, M.; Coppola, C.; Buccella, F.; Cresteil, T.; Mignani, S.; Caminade, A. M.; Costes, J. P.; Majoral, J.-P. Comparative EPR studies of Cu(II)-conjugated phosphorous-dendrimers in the absence and presence of normal and cancer cells. RSC Adv. 2014, 4, 36573–36583.CrossRefGoogle Scholar
  46. [46]
    Ottaviani, M. F.; Cangiotti, M.; Fattori, A.; Coppola, C.; Lucchi, S.; Ficker, M.; Petersen, J. F.; Christensen, J. B. Copper(II) complexes with 4-carbomethoxypyrrolidone functionalized PAMAM-dendrimers: An EPR study. J. Phys. Chem. B 2013, 117, 14163–14172.CrossRefGoogle Scholar
  47. [47]
    Apicella, A.; Soncini, M.; Deriu, M. A.; Natalello, A.; Bonanomi, M.; Dellasega, D.; Tortora, P.; Regonesi, M. E.; Casari, C. S. A hydrophobic gold surface triggers misfolding and aggregation of the amyloidogenic Josephin domain in monomeric form, while leaving the oligomers unaffected. PLoS One 2013, 8, e58794.CrossRefGoogle Scholar
  48. [48]
    Grasso, G.; Tuszynski, J. A.; Morbiducci, U.; Licandro, G.; Danani, A.; Deriu, M. A. Thermodynamic and kinetic stability of the Josephin Domain closed arrangement: Evidences from replica exchange molecular dynamics. Biol. Direct 2017, 12, 2.CrossRefGoogle Scholar
  49. [49]
    Deriu, M. A.; Grasso, G.; Tuszynski, J. A.; Gallo, D.; Morbiducci, U.; Danani, A. Josephin Domain structural conformations explored by metadynamics in essential coordinates. PLoS Comput. Biol. 2016, 12, e1004699.CrossRefGoogle Scholar
  50. [50]
    Deriu, M. A.; Grasso, G.; Licandro, G.; Danani, A.; Gallo, D.; Tuszynski, J. A.; Morbiducci, U. Investigation of the Josephin domain protein–protein interaction by molecular dynamics. PLoS One 2014, 9, e108677.CrossRefGoogle Scholar
  51. [51]
    Soncini, M.; Vesentini, S.; Ruffoni, D.; Orsi, M.; Deriu, M. A.; Redaelli, A. Mechanical response and conformational changes of alpha-actinin domains during unfolding: A molecular dynamics study. Biomech. Model. Mechanobiol. 2007, 6, 399–407.CrossRefGoogle Scholar
  52. [52]
    Garzoni, M.; Cheval, N.; Fahmi, A.; Danani, A.; Pavan, G. M. Ion-selective controlled assembly of dendrimer-based functional nanofibers and their ionic-competitive disassembly. J. Am. Chem. Soc. 2012, 134, 3349–3357.CrossRefGoogle Scholar
  53. [53]
    Popescu, L. M.; Piticescu, R. M.; Doni, G.; Danani, A. Interfacial interactions of Fe3+ with PAMAM dendrimer in different pressure conditions. Molecular dynamics. Rev. Roum. Chim. 2012, 57, 35–38.Google Scholar
  54. [54]
    Deriu, M. A.; Popescu, L. M.; Ottaviani, M. F.; Danani, A.; Piticescu, R. M. Iron oxide/PAMAM nanostructured hybrids: Combined computational and experimental studies. J. Mater. Sci. 2016, 51, 1996–2007.CrossRefGoogle Scholar
  55. [55]
    Boye, S.; Ennen, E.; Scharfenberg, L.; Appelhans, D.; Nilsson, L.; Lederer, A. From 1D rods to 3D networks: A biohybrid topological diversity investigated by asymmetrical flow field-flow fractionation. Macromolecules 2015, 48, 4607–4619.CrossRefGoogle Scholar
  56. [56]
    Tomalia, D. A.; Rookmaker, M. Poly (propylene imine) dendrimers. In Polymer Data Handbook, 2nd ed.; Mark, J. E., Ed.; Oxford University Press: New York, 2009; pp 979–982.Google Scholar
  57. [57]
    Louis-Jeune, C.; Andrade-Navarro, M. A.; Perez-Iratxeta, C. Prediction of protein secondary structure from circular dichroism using theoretically derived spectra. Proteins 2012, 80, 374–381.CrossRefGoogle Scholar
  58. [58]
    Budil, D. E.; Lee, S.; Saxena, S.; Freed, J. H. Nonlinear-least-squares analysis of slow-motion EPR spectra in one and two dimensions using a modified Levenberg–Marquardt algorithm. J. Magn. Reson. Ser. A 1996, 120, 155–189.CrossRefGoogle Scholar
  59. [59]
    Wogulis, M.; Wright, S.; Cunningham, D.; Chilcote, T.; Powell, K.; Rydel, R. E. Nucleation-dependent polymerization is an essential component of amyloid-mediated neuronal cell death. J. Neurosci. 2005, 25, 1071–1080.CrossRefGoogle Scholar
  60. [60]
    Coles, M.; Bicknell, W.; Watson, A. A.; Fairlie, D. P.; Craik, D. J. Solution structure of amyloid β-peptide(1–40) in a water-micelle environment. Is the membrane-spanning domain where we think it is? Biochemistry 1998, 37, 11064–11077.CrossRefGoogle Scholar
  61. [61]
    Boopathi, S.; Kolandaivel, P. Role of zinc and copper metal ions in amyloid β-peptides Aβ1–40 and Aβ1–42 aggregation. RSC Adv. 2014, 4, 38951–38965.CrossRefGoogle Scholar
  62. [62]
    Hornak, V.; Abel, R.; Okur, A.; Strockbine, B.; Roitberg, A.; Simmerling C. Comparison of multiple Amber force fields and development of improved protein backbone parameters. Proteins 2006, 65, 712–725.CrossRefGoogle Scholar
  63. [63]
    Lindorff-Larsen, K.; Piana, S.; Palmo, K.; Maragakis, P.; Klepeis, J. L.; Dror, R. O.; Shaw, D. E. Improved sidechain torsion potentials for the Amber ff99SB protein force field. Proteins 2010, 78, 1950–1958.Google Scholar
  64. [64]
    Jorgensen, W. L.; Chandrasekhar, J.; Madura, J. D.; Impey, R. W.; Klein, M. L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 1983, 79, 926–935.CrossRefGoogle Scholar
  65. [65]
    Lindorff-Larsen, K.; Maragakis, P.; Piana, S.; Eastwood, M. P.; Dror, R. O.; Shaw, D. E. Systematic validation of protein force fields against experimental data. PLoS One 2012, 7, e32131.CrossRefGoogle Scholar
  66. [66]
    Robertazzi, A.; Vargiu, A. V.; Magistrato, A.; Ruggerone, P.; Carloni, P.; de Hoog, P.; Reedijk, J. Copper-1,10-phenanthroline complexes binding to DNA: Structural predictions from molecular simulations. J. Phys. Chem. B 2009, 113, 10881–10890.CrossRefGoogle Scholar
  67. [67]
    Pavan, G. M.; Posocco, P.; Tagliabue, A.; Maly, M.; Malek, A.; Danani, A.; Ragg, E.; Catapano, C. V.; Pricl, S. PAMAM dendrimers for siRNA delivery: Computational and experimental insights. Chem.-Eur. J. 2010, 16, 7781–7795.CrossRefGoogle Scholar
  68. [68]
    Pavan, G. M.; Monteagudo, S.; Guerra, J.; Carrión, B.; Ocaña, V.; Rodríguez-Lopez, J.; Danani, A.; Pérez-Martínez, F. C.; Ceña, V. Role of generation, architecture, pH and ionic strength on successful siRNA delivery and transfection by hybrid PPV-PAMAM dendrimers. Curr. Med. Chem. 2012, 19, 4929–4941.CrossRefGoogle Scholar
  69. [69]
    Jensen, L. B.; Pavan, G. M.; Kasimova, M. R.; Rutherford, S.; Danani, A.; Nielsen, H. M.; Foged, C. Elucidating the molecular mechanism of PAMAM-siRNA dendriplex selfassembly: Effect of dendrimer charge density. Int. J. Pharm. 2011, 416, 410–418.CrossRefGoogle Scholar
  70. [70]
    Pavan, G. M.; Albertazzi, L.; Danani, A. Ability to adapt: Different generations of PAMAM dendrimers show different behaviors in binding siRNA. J. Phys. Chem. B 2010, 114, 2667–2675.CrossRefGoogle Scholar
  71. [71]
    Maingi, V.; Jain, V.; Bharatam, P. V.; Maiti, P. K. Dendrimer building toolkit: Model building and characterization of various dendrimer architectures. J. Comput. Chem. 2012, 33, 1997–2011.CrossRefGoogle Scholar
  72. [72]
    Mukherjee, G.; Patra, N.; Barua, P.; Jayaram, B. A fast empirical GAFF compatible partial atomic charge assignment scheme for modeling interactions of small molecules with biomolecular targets. J. Comput. Chem. 2011, 32, 893–907.CrossRefGoogle Scholar
  73. [73]
    da Silva, A. W. S.; Vranken, W. F. ACPYPE—AnteChamber PYthon parser interfacE. BMC Res. Notes 2012, 5, 367.CrossRefGoogle Scholar
  74. [74]
    Dupradeau, F. Y.; Pigache, A.; Zaffran, T.; Savineau, C.; Lelong, R.; Grivel, N.; Lelong, D.; Rosanski, W.; Cieplak, P. The R.E.D. tools: Advances in RESP and ESP charge derivation and force field library building. Phys. Chem. Chem. Phys. 2010, 12, 7821–7839.CrossRefGoogle Scholar
  75. [75]
    Vanquelef, E.; Simon, S.; Marquant, G.; Garcia, E.; Klimerak, G.; Delepine, J. C.; Cieplak, P.; Dupradeau, F. Y. R.E.D. Server: A web service for deriving RESP and ESP charges and building force field libraries for new molecules and molecular fragments. Nucleic Acids Res. 2011, 39, W511–W517.CrossRefGoogle Scholar
  76. [76]
    Bayly, C. I.; Cieplak, P.; Cornell, W.; Kollman, P. A. A well-behaved electrostatic potential based method using charge restraints for deriving atomic charges: The RESP model. J. Phys. Chem. 1993, 97, 10269–10280.CrossRefGoogle Scholar
  77. [77]
    Bussi, G.; Donadio, D.; Parrinello, M. Canonical sampling through velocity rescaling. J. Chem. Phys. 2007, 126, 014101.CrossRefGoogle Scholar
  78. [78]
    Berendsen, H. J. C.; Postma, J. P. M.; Van Gunsteren, W. F.; DiNola, A.; Haak, J. R. Molecular dynamics with coupling to an external bath. J. Chem. Phys. 1984, 81, 3684–3690.CrossRefGoogle Scholar
  79. [79]
    Nosé, S.; Klein, M. L. Constant pressure molecular dynamics for molecular systems. Mol. Phys. 1983, 50, 1055–1076.CrossRefGoogle Scholar
  80. [80]
    Parrinello, M.; Rahman, A. Polymorphic transitions in single crystals: A new molecular dynamics method. J. Appl. Phys. 1981, 52, 7182–7190.CrossRefGoogle Scholar
  81. [81]
    Hess, B.; Kutzner, C.; van der Spoel, D.; Lindahl, E. GROMACS 4: Algorithms for highly efficient, load-balanced, and scalable molecular simulation. J. Chem. Theory Comput. 2008, 4, 435–447.CrossRefGoogle Scholar
  82. [82]
    Humphrey, W.; Dalke, A.; Schulten, K. VMD: Visual molecular dynamics. J. Mol. Graph. 1996, 14, 33–38.CrossRefGoogle Scholar
  83. [83]
    Ulucan, O.; Jaitly, T.; Helms, V. Energetics of hydrophilic protein–protein association and the role of water. J. Chem. Theory Comput. 2014, 10, 3512–3524.CrossRefGoogle Scholar
  84. [84]
    Grasso, G.; Deriu, M. A.; Prat, M.; Rimondini, L.; Vernè, E.; Follenzi, A.; Danani, A. Cell penetrating peptide adsorption on magnetite and silica surfaces: A computational investigation. J. Phys. Chem. B 2015, 119, 8239–8246.CrossRefGoogle Scholar
  85. [85]
    De Moura, D. C.; Bryksa, B. C.; Yada, R. Y. In silico insights into protein–protein interactions and folding dynamics of the saposin-like domain of Solanum tuberosum aspartic protease. PLoS One 2014, 9, e104315.CrossRefGoogle Scholar
  86. [86]
    Lemkul, J. A.; Bevan, D. R. Assessing the stability of Alzheimer’s amyloid protofibrils using molecular dynamics. J. Phys. Chem. B 2010, 114, 1652–1660.CrossRefGoogle Scholar
  87. [87]
    Kumar, S.; Rosenberg, J. M.; Bouzida, D.; Swendsen, R. H.; Kollman, P. A. The weighted histogram analysis method for free-energy calculations on biomolecules. I. The method. J. Comput. Chem. 1992, 13, 1011–1021.CrossRefGoogle Scholar
  88. [88]
    Gkeka, P.; Angelikopoulos, P.; Sarkisov, L.; Cournia, Z. Membrane partitioning of anionic, ligand-coated nanoparticles is accompanied by ligand snorkeling, local disordering, and cholesterol depletion. PLoS Comput. Biol. 2014, 10, e1003917.CrossRefGoogle Scholar
  89. [89]
    Grasso, G.; Deriu, M. A.; Tuszynski, J. A.; Gallo, D.; Morbiducci, U.; Danani, A. Conformational fluctuations of the AXH monomer of Ataxin-1. Proteins 2016, 84, 52–59.CrossRefGoogle Scholar
  90. [90]
    Kannappan, R.; Rousselin, Y.; Jabri, R. Z.; Goze, C.; Brandès, S.; Guilard, R.; Zrineh, A.; Denat, F. Synthesis, structure and coordination properties of three cyclam-based ligands bearing one scorpionate arm. Inorg. Chim. Acta 2011, 373, 150–158.CrossRefGoogle Scholar
  91. [91]
    Alves, L. G.; Souto, M.; Madeira, F.; Adão, P.; Munhá, R. F.; Martins, A. M. Syntheses and solid state structures of cyclam-based copper and zinc compounds. J. Organomet. Chem. 2014, 760, 130–137.CrossRefGoogle Scholar
  92. [92]
    Lima, L. M. P.; Esteban-Gómez, D.; Delgado, R.; Platas-Iglesias, C.; Tripier, R. Monopicolinate cyclen and cyclam derivatives for stable copper(II) complexation. Inorg. Chem., 2012, 51, 6916–6927.CrossRefGoogle Scholar
  93. [93]
    Dorlet, P.; Gambarelli, S.; Faller, P.; Hureau, C. Pulse EPR spectroscopy reveals the coordination sphere of copper(II) ions in the 1–16 Amyloid-β peptide: A key role of the first two N-terminus residues. Angew. Chem., Int. Ed. 2009, 48, 9273–9276.CrossRefGoogle Scholar
  94. [94]
    Drew, S. C.; Masters, C. L.; Barnham, K. J. J. Alanine-2 carbonyl is an oxygen ligand in Cu2+ coordination of Alzheimer’s disease amyloid-β peptide—Relevance to N-terminally truncated forms. J. Am. Chem. Soc. 2009, 131, 8760–8761.CrossRefGoogle Scholar
  95. [95]
    Drew, S. C.; Noble, C. J.; Masters, C. L.; Hanson, G. R.; Barnham, K. J. Pleomorphic copper coordination by Alzheimer’s disease amyloid-β peptide. J. Am. Chem. Soc. 2009, 131, 1195–1207.CrossRefGoogle Scholar
  96. [96]
    Hureau, C.; Dorlet P. Coordination of redox active metal ions to the amyloid precursor protein and to amyloid-β peptides involved in Alzheimer disease. Part 2: Dependence of Cu(II) binding sites with Aβ sequences. Coord. Chem. Rev. 2012, 256, 2175–2187.CrossRefGoogle Scholar
  97. [97]
    Opazo, C.; Ruiz, F. H.; Inestrosa N. C. Amyloid-β-peptide reduces copper(II) to copper(I) independent of its aggregation state. Biol. Res. 2000, 33, 125–131.CrossRefGoogle Scholar
  98. [98]
    Faller, P.; Hureau, C. Bioinorganic chemistry of copper and zinc ions coordinated to amyloid-β peptide. Dalton Trans. 2009, 1080–1094.Google Scholar
  99. [99]
    Azimi, S.; Rauk, A. On the involvement of copper binding to the N-terminus of the amyloid beta peptide of Alzheimer’s disease: A computational study on model systems. Int. J. Alzheimers Dis. 2011, 2011, 539762.Google Scholar
  100. [100]
    Lv, Z. J.; Roychaudhuri, R.; Condron, M. M.; Teplow, D. B.; Lyubchenko, Y. L. Mechanism of amyloid β-protein dimerization determined using single-molecule AFM force spectroscopy. Sci. Rep. 2013, 3, 2880.CrossRefGoogle Scholar

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

Personalised recommendations