This thesis describes the clinical investigation of a novel treatment strategy for type 2 diabetes mellitus (t2dm) using an antisense oligonucleotide(aon)to inhibit the sglt2 receptor. Furthermore... Show moreThis thesis describes the clinical investigation of a novel treatment strategy for type 2 diabetes mellitus (t2dm) using an antisense oligonucleotide(aon)to inhibit the sglt2 receptor. Furthermore it describes skin effects of oligonucleotides Show less
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
