This thesis describes the development and application of different methods for the construction of 1,2-cis glycosidic bonds, which remains one of the most challenging aspects in synthetic... Show moreThis thesis describes the development and application of different methods for the construction of 1,2-cis glycosidic bonds, which remains one of the most challenging aspects in synthetic carbohydrate chemistry. In Chapter 2 a synthesis of an orthogonally protected 2-acetamido-4-amino-2,4,6-trideoxy-D-galactose (AAT) building block starting from D-glucosamine is outlined. Chapter 3 describes a modular approach towards the synthesis of all possible trimer repeating units of the type 1 capsular polysaccharide of Streptococcus pneumonia, Sp1. The difficulty associated with the efficient stereoselective introduction of _-galacturonic acid bonds was overcome by employing galacturonic acid-[3,6]-lactone building blocks. Chapter 4 describes a study of the reactivity and stereoselectivity of a galacturonic acid-3,6-lactone thioglycosyl donor in comparison with protected galacturonic acid and galactose donors using a series of competition experiments and condensation reactions with different thiophilic activator systems. Chapter 5a describes the application of a panel of C-6 thioether mannosyl donors, a C-6-selenoether donor and a C-6-iodide N-phenyltrifluoroacetimidate mannosyl donor in a series of condensation reactions. The applicability of one of these 1,2-cis-mannosylating agents is the subject of Chapter 5b. Upon condensation of 6-thio-6-deoxy-mannosyl donors reductive removal of the 6-thio functionality provides 1,2-cis rhamnosides. Following this methodology a backbone tetrasaccharide containing alternating _- and _-D-rhamnosides was synthesized. Show less
Meevissen, M.H.J.; Yazdanbakhsh, M.; Hokke, C.H. 2012
Schistosomes are parasitic helminths that cause chronic infections in over 200 million people in tropical and sub-tropical areas around the world. Glycoproteins from the eggs of the parasite... Show moreSchistosomes are parasitic helminths that cause chronic infections in over 200 million people in tropical and sub-tropical areas around the world. Glycoproteins from the eggs of the parasite Schistosoma mansoni induce various immune responses in the human host, including T-cell modulation and granuloma formation. Three major, immunogenic egg glycoproteins have been identified; omega-1, IPSE/_1 and kappa-5. The studies in this thesis have unraveled structural and molecular details of the interaction between these three glycoproteins and innate immune cells of the host. Firstly, we have studied the structural details of the N-glycans expressed on these three glycoproteins. Most notably, omega-1 and IPSE/_1 carry diantennary N-glycans which mainly display Lewis X motifs, while kappa-5 expresses triantennary N-glycans with LDN motifs. Then, we have investigated the interaction of the egg glycoproteins with C-type lectin receptors on antigen-presenting immune cells. We show that specific glycan motifs on the egg glycoproteins determine differential binding to these lectin receptors. Finally, we have investigated functional effects of omega-1 and kappa-5. We show that the Th2-modulating capacity of omega-1 is dependent on both glycan-lectin interactions as well as its RNase activity. We found that kappa-5 contains granuloma-inducing properties, which are partly mediated by its LDN motifs. Show less
Selman, M.H.J.; Hoffmann, M.; Zauner, G.; McDonnell, L.A.; Balog, C.I.A.; Rapp, E.; ... ; Wuhrer, M. 2012
