Susanne Boye

pH-triggered aggregate shape of different generations lysine-dendronized maleimide copolymers with maltose shell.

Glycopolymers are promising materials in the field of biomedical applications and in the fabrication of supramolecular structures with specific functions. For tunable design of supramolecular structures, glycopolymer architectures with specific properties (e.g., controlled self-assembly) are needed. Using the concept of dendronized polymers, a series of H-bond active giant glycomacromolecules with maleimide backbone and lysine dendrons of different generations were synthesized. They possess different macromolecular size and functionality along the backbone. Their peripheral maltose units lead to solubility under physiological conditions and controlled aggregation behavior. The aggregation behavior was investigated depending on generation number, pH value, and concentration. A portfolio of complementary analytical tools give an insight into the influence of the different parameters in shaping a rod-, coil-, and worm-like molecular structure and their controlled aggregate formation. MD simulation helped us to understand the complex aggregation behavior of the linear polymer chain without dendritic units.

An alternative route to dye-polymer complexation study using asymmetrical flow field-flow fractionation.

The goal of the present work is to apply the versatile asymmetrical flow field-flow fractionation (AF4) coupled to UV and light scattering detection for the characterization of hyperbranched poly(ethylene imine) decorated with maltose shell (PEI-Mal) and the polar dye Rose Bengal (RB) in respect to their complexation behaviour. The quantitative determination of the non-complexed dye was carried out using the ultra-filtration effect of AF4 during the focussing phase, whereas the non-bound RB is filtrated and transported out of the channel while the complex of RB and PEI-Mal remains inside. A calibration with UV detector (550 nm) was established and different parameters (e.g. membrane material, molecular weight cut-off and stability of both, pure RB and RB@PEI-Mal complexes in solution) were investigated and verified. Successful reproducibility tests were performed. First complexation studies with the developed method were applied successfully with different mixture compositions of RB and PEI-Mal.

Biohybrid structures consisting of biotinylated glycodendrimers and proteins: influence of the biotin ligand's number and chemical nature on the biotin–avidin conjugation

We present the bioconjugation of avidin as a central and/or bridging building block with mono-, bi- and tetravalent biotinylated glycodendrimers to fabricate defined supramolecular nanostructures for future (bio)medical applications. For this purpose mono-, bi- and tetravalent biotinylated glycodendrimers, decorated with short alkyl-linked or long PEG-linked biotin ligands, were synthesized and characterized by NMR, IR and mass spectrometry and HABA displacement assay. Various techniques (UV/Vis, DLS, TEM, LILBID-MS and AF4) were used in order to obtain information about the structural properties of different conjugates of avidin and mono-, bi- and tetravalent biotinylated glycodendrimers. The biotin ligands spacer length, its chemical structure and the degree of biotin functionalization are essential parameters in the formation of nanostructures with avidin having a controlled composition and size dimension up to 100 nm. Biohybrid structures with avidin as a central unit require monovalent glycodendrimers with PEG-linked biotin, while bi- and tetravalent glycodendrimers with short alkyl-linked biotin ligands are more efficient than their counterparts with longer PEG–biotin ligands in the fabrication of defined biohybrid structures (∅ up to 100 nm) with avidin as a bridging unit. The most dominating key issue, combined with other conjugation issues, is the optimal ligand–receptor stoichiometry to fabricate biohybrid structures with diameter of <20, <30 or up to 100 nm.

Poly(ethylene oxide)-b-poly(3-sulfopropyl methacrylate) Block Copolymers for Calcium Phosphate Mineralization and Biofilm Inhibition

Poly(ethylene oxide) (PEO) has long been used as an additive in toothpaste, partly because it reduces biofilm formation on teeth. It does not, however, reduce the formation of dental calculus or support the remineralization of dental enamel or dentine. The present article describes the synthesis of new block copolymers on the basis of PEO and poly(3-sulfopropyl methacrylate) blocks using atom transfer radical polymerization. The polymers have very large molecular weights (over 10(6) g/mol) and are highly water-soluble. They delay the precipitation of calcium phosphate from aqueous solution but, upon precipitation, lead to relatively monodisperse hydroxyapatite (HAP) spheres. Moreover, the polymers inhibit the bacterial colonization of human enamel by Streptococcus gordonii, a pioneer bacterium in oral biofilm formation, in vitro. The formation of well-defined HAP spheres suggests that a polymer-induced liquid precursor phase could be involved in the precipitation process. Moreover, the inhibition of bacterial adhesion suggests that the polymers could be utilized in caries prevention.

Sphere-Like Protein-Glycopolymer Nanostructures Tailored by Polyassociation.

Key parameters allow a reproducible polyassociation between avidin and biotinylated glycopolymers in order to fabricate defined supramolecular nanostructures for future (bio)medical and biotechnological applications. Thus, the polymerization efficiency of biotinylated glycopolymers in the fabrication of biohybrid structures (BHS) was investigated with regard to the influence of (i) the degree of biotinylation of the dendritic glycoarchitectures, (ii) two biotin linkers, (iii) the dendritic scaffold (perfectly branched vs hyperbranched), and (iv) the ligand-receptor stoichiometry. The adjustment of all these parameters opens the way to fabricate defined sizes of the final biohybrid structures as a multifunctional platform ready for their use in different applications. Various analytical techniques, including purification of BHS, were used to gain fundamental insights into the structural properties of the resulting protein-glycopolymer BHS. Finally, the elucidation of pivotal conformational properties of isolated BHS with defined sizes by asymmetrical flow field flow fractionation study revealed that they mainly possess spherical-/star-like properties. From this study, the fundamental knowledge can be likely transferred to other assemblies formed by molecular recognition processes (e.g., adamantane-β-cyclodextrin).

Poly(ethylene oxide)-based block copolymers with very high molecular weights for biomimetic calcium phosphate mineralization

The present article is among the first reports on the effects of poly(ampholyte)s and poly(betaine)s on the biomimetic formation of calcium phosphate. We have synthesized a series of di- and triblock copolymers based on a non-ionic poly(ethylene oxide) block and several charged methacrylate monomers, 2-(trimethylammonium)ethyl methacrylate chloride, 2-((3-cyanopropyl)-dimethylammonium)ethyl methacrylate chloride, 3-sulfopropyl methacrylate potassium salt, and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide. The resulting copolymers are either positively charged, ampholytic, or betaine block copolymers. All the polymers have very high molecular weights of over 106 g mol−1. All polymers are water-soluble and show a strong effect on the precipitation and dissolution of calcium phosphate. The strongest effects are observed with triblock copolymers based on a large poly(ethylene oxide) middle block (nominal Mn = 100 000 g mol−1). Surprisingly, the data show that there is a need for positive charges in the polymers to exert tight control over mineralization and dissolution, but that the exact position of the charge in the polymer is of minor importance for both calcium phosphate precipitation and dissolution.

Separation of linear and star-shaped polystyrenes by phase distribution chromatography

The phase distribution chromatographic technique was optimized and applied for the separation of linear and star-shaped polystyrene (PS). For this purpose non-crosslinked, ultra high molecular weight PS coated on different supporting materials was used. The stability of the coating under chromatographic conditions was tested by thermo gravimetric analysis and microscopic techniques. The modification of different column packing materials was tested. Separation according to branching was indicated for different molecular weights of linear and star-shaped PS. The resolution of the separation was improved by changing the density of the stationary phase and the temperature. The separation results were supported by cloud point measurements and the determination of the critical conditions for linear and star-polymers at the same molecular weight.

Coil-like Enzymatic Biohybrid Structures Fabricated by Rational Design: Controlling Size and Enzyme Activity over Sequential Nanoparticle Bioconjugation and Filtration Steps

Well-defined enzymatic biohybrid structures (BHS) composed of avidin, biotinylated poly(propyleneimine) glycodendrimers, and biotinylated horseradish peroxidase were fabricated by a sequential polyassociation reaction to adopt directed enzyme prodrug therapy to protein-glycopolymer BHS for potential biomedical applications. To tailor and gain fundamental insight into pivotal properties such as size and molar mass of these BHS, the dependence on the fabrication sequence was probed and thoroughly investigated by several complementary methods (e.g., UV/vis, DLS, cryoTEM, AF4-LS). Subsequent purification by hollow fiber filtration allowed us to obtain highly pure and well-defined BHS. Overall, by rational design and control of preparation parameters, e.g., fabrication sequence, ligand-receptor stoichiometry, and degree of biotinylation, well-defined BHS with stable and even strongly enhanced enzymatic activities can be achieved. Open coil-like structures of BHS with few branches are available by the sequential bioconjugation approach between synthetic and biological macromolecules possessing similar size dimensions.