Organic Chemistry Seminar: Chemical Biology of Cellular Carbohydrates

 

Carbohydrates are involved in a myriad of cellular functions. In the form of glycoconjugates they modulate activity and physicochemical properties of proteins and lipids, and they are themselves involved in molecular recognitions processes. However, our understanding of the underlying mechanisms is just at the beginning and methods for their elucidation need further development. Challenges in current glycobiology include (I) the elucidation of the mechanisms of multivalent carbohydrate-protein interactions and (II) the development of tools to monitor glycan structures in cells and organisms. This lecture gives an overview of our group’s activities in these fields. (I) Combining X-ray crystallography and distance measurements in the nanometer range by EPR spectroscopy using spin-labeled carbohydrates, we were able to unravel the molecular details of carbohydrate-protein interactions.1 (II) For monitoring glycans in different cell lines and in zebrafish, we employed metabolic glycoengineering. To increase the repertoire of existing bioorthogonal ligation reactions, we developed new ligation methods based on the inverse-electron-demand Diels-Alder reaction.2 Since this reaction can be orthogonal to azide-alkyne cycloadditions, detection of two different sugars is possible within one experiment. Fluorescence lifetime imaging microscopy (FLIM) of EGFP-tagged and metabolically labeled proteins exploiting fluorescence resonance energy transfer between EGFP and the labeled glycan enabled the visualization of protein-specific intracellular glycosylation.3