Chemoenzymatic synthesis and immunological studies of Xylosylated N-glycans

Resumen

Glycosylation is one of the most common post-translational modifications in eukaryotic cells. It changes during cell development and differentiation and it is tissue and more importantly, species specific. While core ¿-1,6 fucose and/or terminal sialyl residues are typical mammalian features, most of the plant, insects and parasite derived N-glycans contain core ¿-1,3-fucose, ß-1,2-xylose and other terminal motifs. In mammals, some of these glycan elements are believed to be at least partially involved in the stimulation or regulation of immune responses in parasite infected individuals and in the pathophysiology of food allergens. In this Thesis, the chemoenzymatic synthesis of 39 core xylosylated N-glycans is described. Using glycan microarray-assisted studies, the carbohydrate interaction with biologically relevant glycan binding proteins such as plant lectins and animal C-type lectin receptors has been evaluated. Additionally, glycan microarrays were employed for the screening of anti-carbohydrate antibodies raised against S. mansoni parasites. The immune response induced in patients from endemic areas has been compared and the potential biological role of different glycan families is discussed.