Synthesis and Strucuture of GPIs and GPI-Linked Glycopeptides

许多蛋白质和糖蛋白由糖基磷脂酰肌醇(GGIs)锚定在细胞上，GPI是糖脂家族中的一个家族。因此，GPI和GPI锚定分子在多种生物过程中发挥着重要作用，如人类生殖过程。为了研究这些过程，均相和结构明确的GPI锚定和GPI连接的分子是必要的，但它们很难从自然或通过合成获得。本项目的目标是：1)探索一种基于固相组装的GPI合成新策略，以提高合成效率；2)研究GPI锚定糖肽抗原CD52的化学合成，建立一种广泛适用的制备GPI-肽/糖肽结合物的方法；3)利用合成样品通过核磁共振分析CD52抗原的溶液结构，有助于了解CD52的构效关系。通过这一奖项，有机和高分子化学项目支持韦恩州立大学化学系郭忠武教授的研究。郭教授和他的研究小组将研究GPI和GPI连接的糖肽的合成。通过开发新的有效的合成方法，该项目将大大促进这些结构的可用性，从而对各种生物事件中的GPI锚定的研究以及糖科学中的其他相关领域产生广泛的影响。该研究项目还将在碳水化合物化学这一要求很高的领域为学生提供重要的培训。

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.