Constructing Azide-Labeled Cell Surfaces Using Polysaccharide Biosynthetic Pathways

Cellular perceptions and responses are often initiated by binding events on the cell surface. Carbohydrates have been recognized as central players in these recognition events. Glycosylation also modulates how efficiently viruses, such as human immunodeficiency virus type 1 and influenza A, infect human cells. Glycosylation-mediated recognition events have been studied using targeted gene disruption in mice, mutant cell lines selected for specific glycosylation phenotypes, and small molecule inhibitors. Targeted disruption of glycosylation genes has provided significant insight into the function and diversity of carbohydrates. An alternative approach to studying the biology of carbohydrates, pioneered by Reutter and co-workers, utilizes the conversion of unnatural biosynthetic precursors to unnatural cell surface polysaccharides with altered biological function. This chapter summarizes the use of azido sugars for metabolic labeling of cell surface glycoconjugates. In addition to ManNAc derivatives, analogs of N-acetylglucosamine, fucose, N-acetylgalactosamine, and sialic acid have been tested for metabolic incorporation. Studies of metabolic incorporation and characterization of the cell surface products are also discussed in the chpater.