PhD defence: Chemo-enzymatic synthesis and analysis of isomeric glycans
Glycans, also known as carbohydrates, are an essential component of all living organisms and are, among other things, present on proteins and lipids in the cellular membrane. Glycan structure is not encoded in the genome, opposed to other biopolymers such as RNA and proteins, but is regulated by around 200 glycosyltransferase enzymes. As a result of substrate competition, glycans are generated that vary in composition, linkage positions and configurations. The large heterogeneity and diversity in glycan structure complicates the synthesis and characterization of glycans.
The research described in this dissertation covers the synthesis of well-defined glycans and applies synthetic glycans in the development of analytical methodology for the detailed structural characterization of naturally occurring glycans. Chemically modified glycans are synthesized by employing glycosyltransferase enzymes. These modifications are manipulated to (de)activate certain positions on a glycan and thereby direct glycosyltransferase activity. Traceless removal of these modifications allows the synthesis of complex natural glycans with controlled architecture. These glycans are used to study differences in biological activity between isomeric glycans. Synthetic glycopeptides with various functionalities are used as model substrates to develop a method to release glycans from glycopeptides without damaging the glycan structure itself. This methodology conserves labile glycan modifications that are often lost in glycan analysis. Furthermore, synthetic complex glycans are applied as reference compounds for the development of analytical methodology that can structurally elucidate challenging glycan epitopes.
- Start date and time
- End date and time
- Academiegebouw, Domplein 29
- PhD candidate
- G.M. Vos
- Chemo-enzymatic synthesis and analysis of isomeric glycans
- PhD supervisor(s)
- prof. dr. G.J.P.H. Boons
- More information
- Full text via Utrecht University Repository