EXCEED THE SPACE PROVIDED. Complex carbohydrates elaborate the surfaces of cells, contribute to the extracellular matrix, anddecorate excreted glycoproteins. Here they mediate a wide variety of processes that are essential to the normalexecution of life processes. They also enter into abnormal processes, such as the invasion of pathogens and theoncogenic transformation of normal cells. Understanding the diversity of carbohydrate structure, the molecularbasis for its origin, and the molecular basis for its recognition are extremely important to the diagnosis andtreatment of disease. In this proposal we outline a Research Resource for Integrated Glycotechnology that willserve the community through the development of new approaches to study carbohydrate-protein interactions at amolecular 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 usingthat understanding to intervene in disease processes, requires information on not only the carbohydrates, but alsothe proteins that dictate their synthesis and recognition. Tackling a characterization problem of this magnitudeand complexity requires a diverse set of tools based on a wide range of analytical, biochemical, chemical, andcomputational science. These tools are most useful when integrated to produce an efficient and versatileresource 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 amountsto allow physical and biochemical characterization, introduction of methods for the synthesis of carbohydrateswith sufficient diversity and purity to probe the molecular basis of affinity, the development of new tools for thestructural characterization of the carbohydrate-protein interactions by mass spectrometry and nuclear magneticresonance, and the development of a computational platform for the integration of data into a completemolecular picture of protein-carbohydrate interactions.
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