Engineering synthetic glycoproteins

Post-translational glycosylation of proteins is an extremely complex process, involving large enzymatic cascades leading to many heterogeneous glycoforms. Performing glycosylation using chemical, or chemoenzymatic processes to mimic natural glycoproteins or create synthetic neoglycoproteins, is a challenging synthetic task. Despite the challenges in their production, homogeneous glycoproteins have many potential applications from study of glycobiology to potential therapeutics. This work aims to advance the chemical tools available to produce synthetic homogeneous glycoproteins, using bioorthogonal chemistry. A bifunctional, biorthogonal linker has been developed which combines oxime ligation and strain-promoted azide-alkyne cycloaddition chemistry to functionalise reducing sugars and glycan derivatives for protein attachment. This linker has been used to produce derivatives of the simple and complex oligosaccharides lactose and GM1, and in combination with enzymatic synthetic approaches, the lactose disaccharide has been extended to produce derivatives trisaccharide Gb3.