- Gervay-Hague, Jacquelyn
- University of California - Davis
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- In order to study the role glycolipids play in cell processes, infectious and food borne diseases as well as in infant development, researchers require ready access to pure compounds. Carbohydrate-based high-throughput screening assays such as the use of glass beads to probe genetic disposition to infectious disease shows great potential for the development of diagnostics and therapies. Some biologically relevant beta-linked glycolipids and gangliosides are available from natural sources such as bovine brain or bovine buttermilk, but the lipid component is found as a mixture.
In order to study the molecular basis and physicochemical properties of pathogen/host interactions, the research community requires access to glycolipids with well-defined lipid components.
The specific aims of this application are designed to meet these important needs through the combination of a novel, facile and cost-effective synthetic platform and efficient purification and characterization processes that afford direct access to homogenous glycolipids and oligosaccharides for biological study. The synthetic efforts outlined in this application will support collaborative efforts focused on the identification of glycan motifs from human milk and different organism types. Access to pure glycan lipids will enable screening platforms that measure bacterial binding and metabolism as a function of glycan identity. Highly efficient protocols that capitalize on a transient protecting group strategy will be employed in the synthesis of bioactive beta-linked glycolipids and gangliosides, alpha-linked glycosphingolipids, and stable C-glycoside analogs.
The specific aims include: 1.) Large scale syntheses of beta-galactosyl, glucosyl and lactosyl ceramides using transient protecting groups 2.) Syntheses of Gb3, GM3, GD3, GM1 using a novel sialylation method 3.) Optimization and expansion uronic acid syntheses including GSL1-GSL-4 and 4.) Syntheses of C- linked bacterial glycolipids.
The goals of this application are primarily focused on synthetic efforts however, the application of these materials using novel screening and analytical tools is also briefly described.
PUBLIC HEALTH RELEVANCE: The development of a rapid and efficient synthetic platform for the preparation of glycan lipids is proposed. These compounds are of interest to the biological community due to the prevalent roles they play in human health and nutrition. In particular, glycans known to interact with pathogenic bacteria will be prepared and incorporated into screening assays to be used in food safety applications.
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- For additional information, including history, sub-projects, results and publications, if available, visit the Project Information web page at the National Institutes of Health Research Portfolio Online Reporting Tool (RePORTER) database.
- Funding Source
- Nat'l. Inst. of General Medical Sciences
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- Natural Toxins
- Viruses and Prions
- Bacterial Pathogens
- Chemical Contaminants