Synthetic and Structural Studies of Sperm CD52

本研究计划的目标是精子CD 52糖基磷脂酰肌醇（GPIs）和糖肽以及完整抗原的化学和化学酶法合成，并使用合成样品和NMR方法研究GPI和N聚糖对CD 52肽结构的影响，将使用新的合成策略以适当保护的形式制备CD 52 GPI和糖肽。脱保护将得到游离的GPI和糖肽，而在脱保护之前的选择性偶联将得到完整的CD 52。将通过NMR光谱分析CD 52糖肽和抗原的溶液结构。凯斯西储大学化学系郭忠武教授的精子CD 52糖肽的合成和结构研究得到了有机和大分子化学项目的支持。精子CD 52属于一组特殊的含糖蛋白，通过称为糖基磷脂酰肌醇（GPIs）的分子锚定在细胞膜上，在人类生殖过程中起着关键作用。然而，获得精子CD 52的纯形式的困难严重阻碍了对这种重要化合物的进一步详细研究。该项目旨在通过全合成解决这一问题，并将通过开发GPIs，糖肽和GPI锚定糖肽的新合成方法来推进化学。这些化合物的有效合成，包括特别标记的化合物，将促进结构和生物学研究。合成的CD 52糖肽和抗原的结构分析将扩大GPIs对肽结构影响的知识，结合生物学研究将有助于理解精子CD 52的结构-活性关系。这些结果最终可能有助于理解人类生殖过程。

This research program targets the chemical and chemoenzymatic synthesis of sperm CD52 glycosylphosphatidylinositols (GPIs) and glycopeptides, as well as the intact antigen, and the investigation of the impacts of GPI and Nglycans on the peptide structure of CD52 using synthetic samples and NMR methods.New synthetic strategies will be used to prepare the CD52 GPI and glycopeptides in properly protected forms. Deprotection will afford the free GPI and glycopeptides, while selective coupling prior to deprotection will afford the intact CD52. Solution structures of CD52 glycopeptides and antigens will be analyzed by NMR spectroscopy.Professor Zhongwu Guo, of the Department of Chemistry at Case Western Reserve University, is supported by the Organic and Macromolecular Chemistry Program for his synthetic and structural studies of sperm CD52 glycopeptides. Sperm CD52, which belongs to a special group of sugar-containing proteins that are anchored to cell membranes through molecules known as glycosylphosphatidylinositols (GPIs), plays a critical role in the human reproduction process. However, the difficulty to obtain pure forms of sperm CD52 has severely hindered further detailed studies about this important compound. This project aims at solving the problem through total synthesis and will advance chemistry by developing new synthetic methods for GPIs, glycopeptides and GPI-anchored glycopeptides. The efficient synthesis of these compounds, including specially labeled ones, will facilitate structural and biological studies. The structural analysis of synthetic CD52 glycopeptides and antigens will expand the knowledge regarding the impacts of GPIs on peptide structures, which combined with biological studies will help understand the structure-activity relationships of sperm CD52. The results may ultimately facilitate the understanding of the human reproduction process.