This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The formation of carbohydrate-protein complexes is important in a variety of processes involving the interaction of a cell with its environment. These processes include natural ones such as cell differentiation, cell aggregation, and cell signaling; they also include disease processes such as viral infection, malignancy, and unwanted inflammation. The development of drugs to moderate natural processes and inhibit disease processes begins with accurate structural models for oligosaccharide-protein interactions. These models have been difficult to get by traditional Nuclear Magnetic Resonance (NMR) approaches because of the dearth of short-distance NOE contacts in oligosaccharide-protein complexes. We are developing a number of experiments and analysis tools that allow the determination of orientational constraints as opposed to the traditional distance constraints obtained in NMR studies. The data come largely from residual dipolar couplings that become measurable when protein and oligosaccharide are induced to orient in special field aligned media. Data must be collected on both entities, requiring efforts to deal with collection of data on 1H-13C pairs at natural abundance in oligosaccharides and assignment of 1H-15N pairs in large, or structurally uncharacterized, proteins. Developments are being tested on molecular systems developed within the center as well as systems developed by external collaborators. These include lectin systems (Galectin-3, P-selectin) known to be important in inflammation and in metastasis of malignant cells, as well as enzyme systems (LpxA, GnTV, ST6Gal1) known to be important in the synthesis of the cell surface carbohydrates.
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