Synthesis and Strucuture of GPIs and GPI-Linked Glycopeptides

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Many proteins and glycoproteins are anchored onto cells by glycosylphosphatidylinositols (GPIs), a family of glycolipids. Thus, GPIs and GPI-anchored molecules play an important role in various biological processes, such as human reproductive process. To investigate these processes, homogeneous and structurally well-defined GPI anchors and GPI-linked molecules are necessary, but they are difficult to obtain from nature or by synthesis. The aims of this project are to: 1) investigate a new strategy for GPI synthesis based on solid-phase assembly, which will improve the synthetic efficiency; 2) investigate the chemical synthesis of CD52, a GPI-anchored glycopeptide antigen, to establish a widely useful method for the preparation of GPI-peptide/glycopeptide conjugates; 3) analyze the solution structure of CD52 antigen by means of NMR using synthetic samples, which may help to understand the structure-activity relationships of CD52. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Zhongwu Guo, of the Chemistry Department at Wayne State University. Professor Guo and his research group will study the synthesis of GPI and GPI-linked glycopeptides. By developing new and effective synthetic methods, this project will significantly facilitate the availability of these structures and thus have a broad impact on the study of GPI-anchoring in various biological events and on other related areas in glycoscience as well. This research project will also provide important student training in the demanding field of carbohydrate chemistry.