Chemical and chemoenzymatic synthesis of ganglioside(mimic)s and sulfoglycolipids

Abstract

The research of this thesis is on the chemical and enzymatic syntheses of complex glycolipids. Complex glycolipids, like gangliosides and sulfoglycolipids, can be found in the cell membrane of nearly every cel in our body. We know that they are essential for our nervous- and immune system. Furthermore, higher levels of glycolipids are often found in cancer cells compared to healthy cells. Also, antibodies for glycolipids are known to damage the nervous system in the auto-immune disease Guillain-Barré syndrome. Since a lot is still unknown on the exact functions and interactions of these substances, we searched for a way to obtain the glycolipids. Isolation of glycolipids is difficult, due to their hydrophilic and hydrophobic parts, negative charges and the present mixtures of very similar glycolipids. Chemical and enzymatic synthesis are the best ways to obtain any glycolipid of interest. Enzymatic synthesis is very efficient and provides pure materials, however not all structures can be synthesized yet, due to the lack of the appropriate enzymes. Chemical synthesis is a way to obtain any desired glycolipid, but requires a proper strategy that includes many steps. The pure synthetic glycolipids can be printed onto a slide and interactions with proteins and antibodies can then be studied. This microarray binding study provides a first indication of the roles of these biomolecules in cancer and auto-immune diseases.