Tools and reagents to study polysaccharide and glycolipid matabolism

Abstract

Carbohydrate processing enzymes are essential for a plethora of biological functions and processes. This thesis has focussed on the development of synthetic procedures for the synthesis of molecules that have the potential of being used for either the monitoring or modification of some of these processes. An effective synthesis of globotriaosylsphingosine has been developed. The stereoselective synthesis of an isotopically labeled D-erythro-sphingosine was then utilized for the formation of a labeled globotriaosylsphingosine, which was used as an internal standard in the monitoring of Fabry patients. Furthermore, a series of non-reducing end modified hyaluronan substrates bearing an anomeric fluorogenic leaving group was synthesized. These substrates were synthesized with the aim of being potential probes for the monitoring of the human hyaluronidase Hyal2. Finally, a new methodology was developed for a straightforward synthesis of sugar nucleotides. This methodology is well suited for the synthesis of modified sugar nucleotides, which can be utilized for the investigation of glycosyltransferases.