Glycoscience Tools and Therapeutics

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SUMMARY Carbohydrate-protein interactions mediate important processes in human physiology and pathophysiology, but the study of these important interactions remains challenging and highly specialized. A major contributor to this problem is the weak binding affinity of many carbohydrate-protein interactions, which limits the applicability of many commonly applied biochemical and biophysical techniques (e.g., ELISA, ITC). This can be somewhat rectified if natural or synthetic multivalent ligands can be utilized, but in many cases, molecules of this sort are challenging to synthesize and/or isolate. The development of glycan microarrays has pushed the glycobiology field forward by enabling numerous groundbreaking studies; however, this technology has yet to become widely available and can only be utilized when a carbohydrate binding protein has been identified by other means. As such there is currently a gap between discovery and downstream assays that needs to be filled to push the field forward. In this proposal we are addressing this gap by developing tools that can identify carbohydrate-protein interactions, using techniques that are widely available to the scientific community. The tools that we are developing circumvent the challenge presented by the low affinity carbohydrate-protein interactions by covalently labeling the carbohydrate binding protein in a carbohydrate directed manner. Here, we propose to: (i) advance the utility of this approach; and (ii) apply this approach to ask important questions in biology and to target disease relevant pathways.