Complex carbohydrates are involved in a broad variety of biological phenomena and their involvement in life-threatening processes, in particular, have given this class of natural compounds a tremendous diagnostic and therapeutic potential. To this end, the PI's laboratory have focused its research effort towards carbohydrates associated with diseases that consistently 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 the disease could be facilitated. Consequently, this could lead to the development of effective tools for the prevention, diagnosis, and/or treatment of these diseases. In light of the above, the long- term goal of the PI's research program is to make complex carbohydrates more accessible to general chemical, biochemical, medical and industrial audiences, and thereby keep pace with the exploding area of glycobiology. Proposed herein is the expansion of studies initiated in the PI's laboratory for the development of novel and general methods and strategies for the synthesis of complex glycostructures. At the core of this proposal is the development of new complementary strategies for expeditious oligosaccharide synthesis. The intellectual merit of the proposed research lies in its significant contributions to the field of basic and applied synthetic carbohydrate chemistry upon its successful completion. Precisely, the success of this endeavor will not only advance the field of carbohydrate chemistry but also fundamentally contribute to further development of organic synthesis in general. We trust that the proposed developments will lead to the discovery of novel synthetic methodologies for the efficient synthesis of excellent carbohydrate-based therapeutics. A broader and long-term impact of this work relate to the professional training in preparative organic, carbohydrate, bioorganic, and bioinorganic 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 chemists to synthesize, modify, and analyze organic molecules by means of developing new (`their own') synthetic methodologies and participating in the elaboration of state-of-the-art, multi-step syntheses. Student researchers will also become fully integrated into the scientific community through the preparation of peer-reviewed manuscripts and their attendance in professional meetings. As a consequence of the latter, students will develop better communication skills while also being exposed to scientific discourse outside their focused area of research. Finally, the proposed research will ultimately strengthen interdisciplinary collaborations with biomedical researchers as the synthetic targets of this project display medicinally-relevant biological activity.
The impact of this proposed research to human health is two-fold. First, the novel strategies outlined herein will allow the general public an easy access to the complex oligosaccharides associated with fatal diseases such as cancer and bacterial infections. Without a doubt, the availability of these molecules for biological studies could significantly advance the development of glycotherapeutics. Another long term impact is the professional training received by undergraduate and graduate researchers in the course of this project is expected to leave them equipped to innovate and advance the emerging field of 21st century glycomedicine.
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| Avegno, Elizabeth Alverson-Banks; Hasty, Scott J; Parameswar, Archana R et al. (2013) Reactive thioglucoside substrates for ?-glucosidase. Arch Biochem Biophys 537:1-4 |
| Heuckendorff, Mads; Premathilake, Hemali D; Pornsuriyasak, Papapida et al. (2013) Superarming of glycosyl donors by combined neighboring and conformational effects. Org Lett 15:4904-7 |
| Ganesh, N Vijaya; Fujikawa, Kohki; Tan, Yih Horng et al. (2012) HPLC-assisted automated oligosaccharide synthesis. Org Lett 14:3036-9 |
| Hasty, S J; Demchenko, A V (2012) Glycosyl Thioimidates as Versatile Building Blocks for Organic Synthesis. Chem Heterocycl Compd (N Y) 48: |
| Tsytsarev, Vassiliy; Maslov, Konstantin I; Yao, Junjie et al. (2012) In vivo imaging of epileptic activity using 2-NBDG, a fluorescent deoxyglucose analog. J Neurosci Methods 203:136-40 |
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