Chemoenzymatic synthesis of phosphorylated glycoproteins.
Degree GrantorUniversity of Canterbury
Degree NameDoctor of Philosophy
Phosphorylation of the glycan portion of glycoproteins is an important posttranslational modification. In particular, the presence of mannose-6-phosphate (M6P) residues on high mannose glycans of lysosomal enzymes is important for the transfer of these enzymes to the lysosomes. The synthesis of different types of N-glycan structures containing M6P residues have been reported by various groups. This thesis work concerns the chemoenzymatic synthesis of phosphorylated glycoproteins, wherein M6P containing N-glycans were synthesised chemically and then enzymatically coupled to give homogeneous glycoproteins. Endo-β-N-acetylglucosaminidases (ENGases), have been employed by various research groups for the synthesis of variety of homogeneous glycopeptides and proteins by using oxazolines as activated donors. This thesis reports the synthesis of bis-phosphorylated tetrasaccharide and hexasaccharide oxazoline donors, and the use of ENGases to catalyse their transfer to peptides and proteins.