Synthetic and Structural Studies of Sperm CD52

本研究针对精子CD52糖基磷脂酰肌醇(GPI)和糖肽的化学和化学酶促合成，以及完整的抗原，利用合成样品和核磁共振方法研究GPI和N-糖聚糖对CD52多肽结构的影响。新的合成策略将用于制备具有适当保护形式的CD52 GPI和糖肽。去保护将提供游离的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波谱进行分析。凯斯西储大学化学系郭忠武教授在有机化学和高分子化学计划的支持下，对精子CD52糖肽的合成和结构进行了研究。精子CD52是一组特殊的含糖蛋白质，通过糖基磷脂酰肌醇(GPI)分子锚定在细胞膜上，在人类生殖过程中发挥着关键作用。然而，获得纯净形式的精子CD52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来解决这一问题，并将通过开发新的GPI、糖肽和GPI锚定糖肽的合成方法来促进化学的发展。这些化合物的高效合成，包括特殊标记的化合物，将有助于结构和生物学研究。对合成的CD52糖肽和抗原的结构分析将扩大对GPI对肽结构影响的认识，结合生物学研究将有助于理解精子CD52的结构与活性关系。这一结果最终可能有助于理解人类的生殖过程。

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.