Development and Application of Surface-Tethered Iterative Carbohydrate Synthesis

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Project Summary/Abstract Complex carbohydrates are involved in a broad variety of biological phenomena and their involvement in disease processes, in particular, have given this class of natural compounds a tremendous diagnostic and therapeutic potential. To this end, the PI's and co-PI's laboratories have focused their research efforts towards carbohydrates associated with diseases that rank among the top 10 leading causes of death worldwide, i.e. cancer, pneumococcal disease, septicemia, and Alzheimer's disease. At the core of this effort is the belief that if a comprehensive knowledge of the structure, conformation, and properties of these carbohydrates were available, elucidation of the mechanisms for the pathogenesis of these diseases could be facilitated. Consequently, this could lead to the development of effective tools for the prevention, diagnosis, and/or treatment of these diseases. The long-term goals of the PI's and co-PI's research programs are to make complex carbohydrates more accessible to general chemical, biochemical, medical and industrial audiences, and thereby keep pace with the exploding areas of glycobiology and related health sciences. Proposed herein is the expansion of studies initiated in our laboratories for the development of novel high-throughput technologies for oligosaccharide and glycoconjugate synthesis. At the core of this proposal is the development of a new strategy for supported synthesis called STICS (Surface-Tethered Iterative Carbohydrate Synthesis). The intellectual merit of the proposed research lies in its significant contributions to the field of basic and applied synthetic carbohydrate, surface, and nanomaterial chemistries upon its successful completion. Precisely, the success of this endeavor will not only advance the field of chemistries mentioned, but also fundamentally contribute to further development of glyco- and nanotechnology in general. We trust that the proposed developments will lead to the discovery of novel methodologies for the efficient synthesis and high throughput screening of carbohydrate-based libraries and therapeutics. A broader and long-term impact of this work relate to the professional training in surface, preparative organic, carbohydrate, bioorganic, and materials chemistry that undergraduate, graduate and post-doctoral research participants will receive. In addition, the multidisciplinary nature of the proposed research will allow students to expand their scientific base in an intellectual and practical sense. During their laboratory experience they will learn important tools that allow obtain, modify, and analyze organic molecules and nanomaterials by means of developing new methodologies and participating in the elaboration of state-of-the-art, multi-step syntheses. Student researchers will also become integrated into the scientific community through the preparation of manuscripts and attendance at professional meetings. As a consequence, students will develop better communication skills while also being exposed to scientific discourse. Finally, the proposed research will ultimately strengthen interdisciplinary collaborations with biomedical researchers.