| For the work described in this dissertation, I adapt a chimeric expression system to explore the synthetic properties (specificity and selectivity) of glycosyltransferases.; Despite the abundance of complex carbohydrate structures in nature, their study in therapeutics and biology is severely limited by access to suitable quantities of complex carbohydrates, synthetic or otherwise, with which to initiate study. Automated solid-phase methodologies have revolutionized protein and nucleic acid science, but decades of synthetic research have yet to provide robust methods for automated oligosaccharide synthesis. This hindrance is a consequence of the carbohydrate structure itself: monosaccharides contain several hydroxyl groups of similar reactivity. To synthesize even a simple oligosaccharide, each hydroxyl group must be correctly distinguished from the others in order to obtain the correct product. Assuring the correct regiochemistry in the hydroxyl selection process is tedious, and involves the shuffling of dozens of differential protecting groups, even for the synthesis of a short oligomer.; The increasing complexity of synthetic carbohydrate chemistry stands in stark contrast to what nature has been able to accomplish with simplicity and elegance. Glycosyltransferases, the enzymes responsible for catalyzing the formation of glycosidic bonds in nature, feature exacting stereo- and regioselectivity and catalyze their reactions under mild conditions. |
