Schistosomiasis is caused by blood-dwelling parasitic trematodes of the genus Schistosoma and is classified by the WHO as the second most socioeconomically devastating parasitic disease, second... Show moreSchistosomiasis is caused by blood-dwelling parasitic trematodes of the genus Schistosoma and is classified by the WHO as the second most socioeconomically devastating parasitic disease, second only to malaria. Schistosoma expresses a complex array of glycans as part of glycoproteins and glycolipids that can be targeted by both the adaptive and the innate part of the immune system. Some of these glycans can be used for diagnostic purposes. A subgroup of schistosome glycans is decorated with unique alpha-(1-2)-fucosides and it has been shown that these often multi-fucosylated fragments are prime targets for antibodies generated during infection. Since these alpha-(1-2)-fucosides cannot be obtained in sufficient purity from biological sources, we set out to develop an effective route of synthesis towards alpha-(1-2)-oligofucosides of varying length. Here we describe the exploration of two different approaches, starting from either end of the fucose chains. The oligosaccharides have been attached to gold nanoparticles and used in an enzyme-linked immunosorbent assay ELISA and a microarray format to probe antibody binding. We show that binding to the oligofucosides of antibodies in sera of infected people depends on the length of the oligofucose chains, with the largest glycans showing most binding. Show less
Goblyos, A.; Schimmel, K.J.M.; Valentijn, A.R.P.M.; Fathers, L.M.; Cordfunke, R.A.; Chan, H.L.; ... ; Hartigh, J. den 2013
This thesis describes the synthesis of oligonucleotide conjugates by means of the strain induced [2+3] dipolar cycloaddition is described. To this end, dibenzocyclooctyne containing phosphoramidite... Show moreThis thesis describes the synthesis of oligonucleotide conjugates by means of the strain induced [2+3] dipolar cycloaddition is described. To this end, dibenzocyclooctyne containing phosphoramidite building blocks were synthesized. These building blocks were subsequently used in the solid phase synthesis of RNA and DNA oligonucleotides yielding dibenzocyclooctyne containing oligonucleotides. These oligonucleotides were used in strain induced cycloadditions with a variety of azides e.g. fluorescent labels, oligosaccharides, oligopeptides and bovine serum albumin yielding the corresponding conjugates. Additionally, the synthesis of D-arabinose and D-ribose derived C-glycosides is described. These nucleoside derivatives were obtained from D-ribose and D-arabinose C-1 substituted hemi-ketals in BF3OEt2-triethyl silane mediated reductions. The results and mechanism regarding the stereoselectivity in these reductions are discussed. Show less
