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A. Poschalko:
"Entwicklung neuer spezifischer Adsorbenzien auf Kohlenhydrat Methacrylat Basis zur extrakorporalen Blutreinigung ";
Betreuer/in(nen), Begutachter/in(nen): H. Gruber, J. Fröhlich; E 163 Institut für Angewandte Syntheschemie, 2003.

A variety of specific adsorbers based on carbohydrate methacrylates for the extracorporal purification of human blood has been developed. Acting as hydrophilic matrix, a novel sucrose based polymer support has been synthesized. In order to control the morphology of such resins during aqueous suspension polymerization, protected (hydrophobic) monomer mixtures have been prepared by esterification of 2,1´:4,6-di-O-isopropylidene sucrose (degree of substitution = 1.6-3.5). These have been polymerized in aqueous suspension using different porogens to yield hydrophilic spherical polymer beads of various morphology after subsequent removal of the protecting groups. The performance of sucrose based polymer resins have been compared with alternative hydrophilic polymer matrices based on glucose methacrylate, polyvinylalcohol, and poly(ethylene glycol), as well as carbohydrate-based microspheres. For the immobilization of appropriate ligands to the supports, different techniques for the activation of hydroxy groups have been investigated. These included epoxidation, cyanogen bromide activation, NHS-esters, the introduction of amino groups via the Mitsunobu reaction, and reductive amination after periodate oxidation of the carbohydrate moieties. Aromatic amino acids, a fibrinogen binding pentapeptide, several TNF-?-binding peptides, and anti-TNF-?-antibodies have been immobilized to activated matrices of different morphology. Peptide ligands have been either coupled to the polymer support or directly synthesized on sucrose-based resins according to the Fmoc/tBu strategy after silylation of remaining hydroxy groups. The adsorption capacity and selectivity of the resulting adsorbers have been studied for the specific elimination of IgG, fibrinogen, and TNF-? respectively. The strong impact of morphology and chemistry of the resins on the affinity performance has been demonstrated.