The influence of densely organized maltose shells on the biological properties of poly(propylene imine) dendrimers: New effects dependent on hydrogen bonding

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Barbara Klajnert - , Lodz University of Technology (Autor:in)
  • Dietmar Appelhans - , Leibniz-Institut für Polymerforschung Dresden (Autor:in)
  • Hartmut Komber - , Leibniz-Institut für Polymerforschung Dresden (Autor:in)
  • Nina Morgner - , Universitätsklinikum Frankfurt (Autor:in)
  • Simona Schwarz - , Leibniz-Institut für Polymerforschung Dresden (Autor:in)
  • Sven Richter - , Leibniz-Institut für Polymerforschung Dresden (Autor:in)
  • Bernhard Brutschy - , Universitätsklinikum Frankfurt (Autor:in)
  • Maksim Ionov - , National University of Uzbekistan named after Mirzo Ulugbek (Autor:in)
  • Anatoly K. Tonkikh - , National University of Uzbekistan named after Mirzo Ulugbek (Autor:in)
  • Maria Bryszewska - , Lodz University of Technology (Autor:in)
  • Brigitte Voit - , Leibniz-Institut für Polymerforschung Dresden (Autor:in)

Abstract

Maltose-modified poly(propylene imine) (PPI) dendrimers were synthesized by reductive amination of unmodified second- to fifth-generation PPI dendrimers in the presence of excess maltose. The dendrimers were characterized by using H-1 NMR C-13 NMR, and I R spectroscopies; laser-induced liquid beam ionization/desorption mass spectrometry; dynamic light scattering analyses; and polyelectrolyte titration. Their scaffolds have enhanced molecular rigidity and their outer spheres, at Which two maltose units are bonded to the former primary amino groups on the Surface, have hydrogen-bond-forming properties. Furthermore, the structural features reveal the presence of a dense shell. Experiments involving encapsulation (1-anilinonaphthalene-8-sulfonic acid) and biological properties (hemolysis and interactions with human serum albumin (HSA) and prion peptide 185-208) were performed to compare the modified with the unmodified dendrimers. These experiments gave the following results: 1) The modified dendrimers entrapped a low-molecular-weight fluorescent dye by means of a dendritic box effect, in contrast to the interfacial uptake characteristic of the unmodified PPI dendrimers. 2) Both low- and high-generation dendrimers containing maltose units showed markedly reduced toxicity. 3) The desirable features of bio-interactions depended on the generation of the dendrimer; they were retained after maltose substitution, but were now mainly governed by nonspecific hydrogen-bonding interactions involving the maltose units. The modified dendrimers interacted with HSA as strongly as the parent compounds and appeared to have potential use as antiprion agents. These improvements will initiate the development of the next platform of glycodendrimers in which apparently contrary properties can be combined, and this will enable, for example, therapeutic products such as more efficient and less toxic anti-amyloid agents to be synthesized.

Details

OriginalspracheEnglisch
Seiten (von - bis)7030-7041
Seitenumfang12
FachzeitschriftChemistry-a European Journal
Jahrgang14
Ausgabenummer23
PublikationsstatusVeröffentlicht - 2008
Peer-Review-StatusJa
Extern publiziertJa

Externe IDs

PubMed 18576443
Scopus 53849139796
ORCID /0000-0002-4531-691X/work/148607757

Schlagworte

Schlagwörter

  • Dendrimers, Hydrogen bonds, Oligosaccharides, Peptides, Poly(propylene imine), Proteins