Complex carbohydrates elaborate the surfaces of cells, contribute to the extracellular matrix, and decorate excreted glycoproteins. Here they mediate a wide variety of processes that are essential to the normal execution of life processes. They also enter into abnormal processes, such as the invasion of pathogens and the oncogenic transformation of normal cells. Understanding the diversity of carbohydrate structure, the molecular basis for its origin, and the molecular basis for its recognition are extremely important to the diagnosis and treatment of disease. In this proposal we outline a Research Resource for Integrated Glycotechnology that will serve the community through the development of new approaches to study carbohydrate-protein interactions at a molecular level and the dissemination of these approaches through collaborative, service, and training activities. Characterization of carbohydrate-protein interactions at a molecular level is not an easy task. Carbohydrate structures are in themselves very diverse. Moreover, understanding their interactions, and using that understanding to intervene in disease processes, requires information on not only the carbohydrates, but also the proteins that dictate their synthesis and recognition. Tackling a characterization problem of this magnitude and complexity requires a diverse set of tools based on a wide range of analytical, biochemical, chemical, and computational science. These tools are most useful when integrated to produce an efficient and versatile resource that can answer questions that arise with the discovery of new carbohydrate-protein interacting systems. Proposed efforts include development of techniques for the production of proteins in adequate amounts to allow physical and biochemical characterization, introduction of methods for the synthesis of carbohydrates with sufficient diversity and purity to probe the molecular basis of affinity, the development of new tools for the structural characterization of the carbohydrate-protein interactions by mass spectrometry and nuclear magnetic resonance, and the development of a computational platform for the integration of data into a complete molecular picture of protein-carbohydrate interactions.
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