Ingrid 't Hart

111 Summary / Samenva�ng 6 remaining glycosyla�ons were performed in DCM in the presence of TMSOTf and 4 Å MS at -40 °C to -70 °C, providing pure β-anomeric selec�vity and yields between 40% - 72%. A�er deprotec�on and sulfa�on of SM1a-core3, this sulfoglycolipid analog will be studied for its HAE3 binding proper�es in a glycan microarray. Chapter 5 Gangliosides and mimics thereof, are not just associated with cancer, but also with auto- immune diseases. Guillian-Barré syndrome (GBS) is such an autoimmune disease, where the peripheral neurons are mainly affected, resul�ng in muscle weakness to various degrees. One third of GBS cases is triggered by Campylobacter jejuni infec�ons. C. jejuni carries ganglioside mimics on its membrane glycan lipooligosaccharides (LOS) which are thought to elicit cross-reac�ve an�bodies towards human endogenous gangliosides. An�bodies towards various the ganglio-series gangliosides, such as GM1a, GM1b and GD1a, have been detected in GBS serum. These gangliosides are mainly present in the peripheral nervous system, partly explaining the symptoms in this disease. In this chapter we described the synthesis of ganglioside mimics to study binding pa�erns of these serum an�ganglioside an�bodies. The smallest difference of bacterial ganglioside mimics and endogenous ganglioside is the monosaccharide L- glycero -D-manno-heptose (Hep). Heptose is solely found in gram-nega�ve bacteria and possibly plays a role in triggering an�ganglioside an�body forma�on. Therefore, we designed a chemoenzyma�c approach to synthesize heptose-ganglioside mimics. Our synthe�c approach started with the chemical glycosyla�on of a galactosyl donor with a heptose acceptor, to form the desired Galβ1,3Hep disaccharide. A�er global deprotec�on, the disaccharide was subsequently extended by bacterial enzymes PmST1 to form Hep-GM3, CgtA to form Hep-GM2 and CgtB to form Hep-GM1. It was observed that the enzyme CgtA quickly lost ac�vity and the lysate should be directly used a�er expression. All structures were equipped with an aminopentyl linker for microarray immobiliza�on. The synthesized ganglioside mimics and the ganglioside oligosaccharides will be studied for their serum an�ganglioside an�body binding proper�es in a glycan microarray.