Ingrid 't Hart

95 Chemoenzyma�c synthesis of heptose-ganglioside mimics 5 Chapter 5 Chemoenzyma�c synthesis of C. jejuni heptose-ganglioside mimics to study an�body binding pa�erns in Guillain- Barré Syndrome Abstract : Guillian-Barré syndrome (GBS) is an autoimmune disease mainly affec�ng peripheral neurons, re- sul�ng in muscle weakness. One third of GBS cases is triggered by a Campylobacter jejuni infec�on. The lipoo- ligosaccharides (LOS) in the outer membrane of C. jejuni can contain ganglioside mimics, which are thought to trigger cross-reac�ve an�bodies for human endogenous gangliosides. The aimof this study is to assess binding of truncated LOS structures and endogenous gangliosides to GBS serum an�bodies. The smallest difference between LOS and natural gangliosides is the monosaccharide L-glycero-D-manno-heptose (Hep). Therefore, heptosyl-ganglioside mimics where synthesized by a chemoenzyma�c approach, star�ng with the chemical synthesis of a Galβ1,3Hep disaccharide. Further enzyma�c extensions by PmST1, CgtA and CgtB provided Hep- GM3, Hep-GM2 and Hep-GM1. All structures were equipped with an aminopentyl linker for microarray im- mobiliza�on. Glycan microarray studies will reveal the effect of microbial-specific heptose on an�ganglioside an�body binding.