Chemical tools to study eukaryotic protein glycosylation

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Glycoconjugates are key biomolecular structures within organisms that are composed of several different interlinked sugar units, most commonly attached to either lipids or proteins. The allocation of approximately 300 genes within the human genome to the proper stepwise assembly and disassembly of glycoconjugates highlights the important roles played by diverse glycoconjugates. The purpose of this regulated structural diversity of glycoconjugates lies in their ability to modulate protein function, mediate molecular interactions, as well as to alter the physical properties and stability of proteins. A striking series of findings in the past few years have suggested that protein glycosylation acts directly to regulates intra- and intercellular signaling and transcription. Remarkably, despite the continuing growth of glycobiology as a prominent and active field of research, the tools available to researchers in this area as compared to other fields are far more limited. To address this gap, we focus in this program on developing chemical tools to aid study of three less investigated forms of glycosylation. Although the glycoconjugates we are interested in have been known for over 20 years, there has been limited progress in elucidating their functional roles in biology. This limited progress stems, in large part, from the lack of molecular and chemical tools available for probing the roles of these glycan structures and the enzymes that process them. Accordingly, the short term program of research described here involves the development of a number of research tools to facilitate decoding the molecular role of these forms of O-glycosylation and to evaluate the activities of the enzymes responsible for processing these glycans. The long term aim of our research group is to provide the glycoscience community with useful tools and thus increase understanding of the functional importance of different forms of glycosylation.