title: The influence of densely organized maltose shells on the biological properties of poly(propylene imine) dendrimers: new effects dependent on hydrogen bonding.
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 (1)H NMR, (13)C NMR, and IR 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 antiamyloid agents to be synthesized.
authors.affiliation: Department of General Biophysics, University of Lodz, 12/16 Banacha Street, Lodz, Poland. aklajn@biol.uni.lodz.pl
authors.forename: Barbara
authors.initials: B
authors.lastname: Klajnert
authors.forename: Dietmar
authors.initials: D
authors.lastname: Appelhans
authors.forename: Hartmut
authors.initials: H
authors.lastname: Komber
authors.forename: Nina
authors.initials: N
authors.lastname: Morgner
authors.forename: Simona
authors.initials: S
authors.lastname: Schwarz
authors.forename: Sven
authors.initials: S
authors.lastname: Richter
authors.forename: Bernhard
authors.initials: B
authors.lastname: Brutschy
authors.forename: Maksim
authors.initials: M
authors.lastname: Ionov
authors.forename: Anatoly K
authors.initials: AK
authors.lastname: Tonkikh
authors.forename: Maria
authors.initials: M
authors.lastname: Bryszewska
authors.forename: Brigitte
authors.initials: B
authors.lastname: Voit
mesh_terms: D000817:Anilino Naphthalenesulfonates / Q000737:chemistry; D001388:Aziridines / Q000737:chemistry*; D050091:Dendrimers / Q000737:chemistry* / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008320:Maltose / Q000737:chemistry*; D013058:Mass Spectrometry; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry; D012709:Serum Albumin / Q000737:chemistry; D013053:Spectrophotometry
chemical_list: D000817:Anilino Naphthalenesulfonates; D001388:Aziridines; D050091:Dendrimers; D010455:Peptides; D012709:Serum Albumin; C027132:1-anilino-8-naphthalenesulfonate; D008320:Maltose; C031132:propyleneimine