The carbohydrate chains displayed on proteins and lipids mediate a broad range of physiological and pathological events on cell surfaces as well as in cells. Hence, the intermolecular interaction systems involving the sugar chains could be potential therapeutic targets for various diseases. In addition, protein glycosylation is now considered to be one of the most important factors in the design and development of biopharmaceuticals currently typified by antibody medicine. To facilitate the design of drugs targeting the carbohydrate recognition systems, atomic description of carbohydrate-protein and carbohydrate-carbohydrate interactions are highly desirable.
In this presentation, I will outline our approaches for characterizing conformational dynamics and interactions of glycoconjugates using NMR spectroscopy in conjunction with other biophysical and biochemical techniques. To reap maximum benefit of NMR approaches, we have established techniques for overexpression of homogeneous oligosaccharides with isotope labeling, which were chemically tagged with paramagnetic probes as sources of long-distance information. We demonstrate that lanthanide-tagging offers a new tool for experimental validation of dynamic conformational ensembles of oligosaccharides derived from molecular dynamics simulations. This presentation will also provide an NMR view of ganglioside clusters as platforms for pathological molecular events involved in onset and promotion of neurodegenerative disorders including Alzheimer’s disease. These approaches will allow new possibilities for structural studies on glycoconjugates of clinical and pharmaceutical interests.