Synthetic and Structural Studies of Sperm CD52

本研究计划以化学和化学酶合成精子CD52糖基磷脂酰肌醇（GPI）和糖肽以及完整抗原为目标，利用合成样品和核磁共振方法研究GPI和糖聚糖对CD52肽结构的影响。新的合成策略将用于制备适当保护形式的CD52 GPI和糖肽。去保护将提供游离GPI和糖肽，而在去保护之前的选择性偶联将提供完整的CD52。CD52糖肽和抗原的溶液结构将通过核磁共振光谱分析。郭忠武教授，凯斯西储大学化学系教授，获有机与大分子化学项目资助，主要从事精子CD52糖肽的合成和结构研究。精子CD52属于一组特殊的含糖蛋白，通过被称为糖基磷脂酰肌醇（gpi）的分子固定在细胞膜上，在人类生殖过程中起着关键作用。然而，难以获得纯形式的精子CD52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来解决这一问题，并将通过开发新的合成gpi、糖肽和gpi锚定糖肽的方法来推进化学。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。对合成的CD52糖肽和抗原进行结构分析，将扩大对GPIs对肽结构影响的认识，并与生物学研究相结合，将有助于了解精子CD52的构效关系。这些结果可能最终促进对人类生殖过程的理解。

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.