Papers
Interactions between dendrimers and heparin and their implications for the anti-prion activity of dendrimers
co-authored with Michela Cangiotti, Sara Calici, Maksim Ionov, Jean Pierre Majoral, Anne-Marie Caminade, Josep Cladera, Maria Bryszewska and Maria Francesca Ottaviani
Heparin is involved in the pathogenesis of prion diseases, affecting the process of fibril formation. It has been shown that whether it accelerates or inhibits fibrilogenesis depends on its
concentration: prion peptide PrP 185-208 aggregates in the presence of 0.04 mg ml-1 heparin, but concentrations ten times lower or higher cause no aggregation. Polyamidoamine, polypropyleneimine and phosphorus dendrimers that previously exhibited anti-prion activity have been shown to interact with heparin. The interactions between cationic dendrimers and anionic heparin are mainly electrostatic. The present study shows that these interactions are indirectly responsible for the inhibition or enhancement of fibril formation by dendrimers.
LikeThe Influence of Densely Organized Maltose Shells on the Biological Properties of Poly(propylene imine) Dendrimers: New Effects Dependent on Hydrogen Bonding
co-authored with Dietmar Appelhans, Hartmut Komber, Nina Morgner, Simona Schwarz, Sven Richter, Bernhard Brutschy, Maksim Ionov, Anatoly K. Tonkikh, Maria Bryszewska, and Brigitte Voit
Maltose-modified poly(propyleneimine) (PPI) dendrimers were synthesized by reductive amination of unmodified second- to fifth-generation PPI dendrimers in the presence of excess maltose.T he dendrimers were characterized by using 1H NMR, 13C NMR, and IR spectroscopies; laserinduced 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 hydrogenbond-
forming properties.Furthermore, the structural features reveal the presence of a dense shell.Exper iments 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.T hese 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 antiamyloid agents to be synthesized.
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