Ingrid 't Hart

17 Introduc�on 1 Figure 7. Molecular mimicry of the lipooligosaccharides (LOS) in the outer membrane of C. jejuni triggers an immune response where an�ganglioside an�bodies are formed. These an�ganglioside an�bodies can become cross-reac�ve towards endogenous gangliosides on myelin and axon neuronal cells. 1.4 Chemical and chemoenzyma�c synthesis of GSL(mimic)s. Studying GSL interac�ons more closely requires homogeneous pure glycolipids. However, isola�on of pure GSLs is a tedious job and o�en results in heterogeneous mixtures. 86,87 Chemical or enzyma�c synthesis would provide a way to obtain sufficient pure GSL glycolipids. S�ll, glycolipid synthesis offers quite some challenges over glycan synthesis. The lipid residue adds addi�onal func�onal groups, such as an alkene, which can lead to side reac�ons during glycosyla�on or (de)protec�ons. Furthermore, ceramide (and sphingosine to a lesser extend) is a glycosyl acceptor with poor reac�vity. 88,89 Not unimportantly, introducing a lipid moiety will affect the solubility of the GSL substrate, especially in the deprotected form. Nonetheless, some strategies have been developed to overcome some of the aformen�oned problems and will be discussed in this chapter and are summarized in Scheme 1. Recently, a chemoenzyma�c strategy was developed where lactosylsphingosine (Lac-Sph) is synthesized chemically, followed by enzyma�c extensions (Scheme 1A). 90 With this strategy, a set of ganglio-series GSLs has been synthesized by bacterial glycosyltransferases. The sphingosine analogues were purified on C18 SPE cartridges followed by coupling of a fa�y acid to the sphingosine to form the ceramide. It was found that commonly used α2,3-sialyltransferase PmST1 was not suitable for glycolipid substrates. Nonetheless, another bacterial enzyme (PmST3) was found to perform this reac�on. Another enzyme, CgtA, showed reduced ac�vity on glycolipids compared to the free glycans. 90 A second chemoenzyma�c approach requires the chemical or C. Jejuni Neuronal cell Antiganglioside antibodies cell membrane GM1a LOS