New strategies for expeditious oligosaccharide synthesis

University Of Missouri-St. Louis, Saint Louis MO

Investigators

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Abstract

DESCRIPTION (provided by applicant): New Strategies for Expeditious Oligosaccharide Synthesis Functions of complex carbohydrates related to a broad variety of biological phenomena and their involvement in life-threatening processes, in particular, have given this class of natural compounds a tremendous scientific, diagnostic and therapeutic potential. To this end, the PI's laboratory has focused its effort toward carbohydrates associated with diseases that rank among the top 10 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 pathogenesis of the disease could be facilitated. Consequently, this could lead to the development of effective tools for the prevention, diagnosis, and treatment of these diseases. Proposed herein is the expansion of studies initiated in the PI's laboratory for the development of novel techniques for the synthesis of complex carbohydrates. At the core of this proposal is the development of new strategies for orthogonal oligosaccharide synthesis. The rationale for these studies is that once a general methodology has been established, it should be possible to use these protocols to design the syntheses of various biologically important or therapeutically relevant compounds. A vast majority of natural complex carbohydrates contain monomeric units connected via O-glycosidic linkages into oligomeric glycostructures, oligosaccharides. Therefore, the studies proposed herein are also expected to be of broad methodological and practical value to all scientists working with bioorganic substances Upon completion of the proposed research program, we expect to have established novel concepts for rapid oligosaccharide assembly and to have developed reliable toolkits applicable to the synthesis of a broad range of complex glycostructures. The PI's major commitment is to maintain a vigorous meritorious research program in the area of synthetic carbohydrate chemistry and allied disciplines that will prepare students to be creative, productive researchers capable of building essential bridges among chemistry, biology and medicine. It has been the PI's belief that exciting scientific discoveries will simplify the synthesis of complex oligosaccharides and glycoconjugates and help to incorporate novel insights into the curriculum as learning tools. PUBLIC HEALTH RELEVANCE: The impact of the proposed research program to human health is two-fold. First, the novel synthetic strategies outlined herein will allow for streamlining the synthesis of complex carbohydrates associated with many fatal diseases including cancer and bacterial infections. Without a doubt, the availability of these molecules for biological studies could significantly advance the development of carbohydrate-based therapeutic and diagnostic agents. Another long-term impact is the exposure undergraduate and graduate researchers will have to meritorious research during the course of this project, which is expected to leave them well equipped to innovate and advance various health-related disciplines in the 21st century.