Funktionelle Modelle zur Untersuchung von Kohlenhydrat-Protein-Wechselwirkungen: Synthese und Testung von Glykokonjugat-Mimetika
In the first part of the thesis, a new concept for the synthesis of glycodendrimers is described, using di-allyl-substituted carbohydrate building blocks as branching units and glycosylation as the ligation step. For the activation of the allyl groups, two methods were tested: the hydroboration/oxidation sequence and the radical addition of mercaptoethanol. This led to two spacer-linked tri- and four heptasaccharides. They showed moderate valence-corrected enhancement (factor 5-50) in the inhibition of mannose-specific bacterial adhesion of E. coli in an ELISA compared to methyl mannoside. Furthermore, again applying the radical thiol-addition procedure with longchain mercaptanes, mannose-based glycolipidomimetics could be synthesised. This synthetic strategy is appealing because of its simplicity and high yields. The aim of the second part of the thesis was the development of a lectin ligand of defined rigidity to allow the investigation of carbohydrate–protein interactions after immobilisation of this ligand and SPR measurements. The ligand was designed taking into account the X-ray structure of the well-known lectin MPA. A series of neoglycopeptides consisting of 14–24 amino acids could be synthesised on solid support. They carry free amino groups, which can be used for immobilisation to allow SPR measurements, which will have to be carried out to study binding of the prepared neoglycopeptides to the lectin MPA. During this work, further interesting carbohydrate-amino acid conjugates with unusual linking patterns could be generated. These compounds are interesting building blocks for peptide synthesis, which can be useful for investigating the influence of structure on lectin binding properties of such neoglycopeptides.
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