Organic Synthesis of Glycoprotein Structural Motifs

本研究的目的是开发糖蛋白聚糖和相关分子探针的合成方法。得到以下结果.天冬酰胺连接的糖蛋白聚糖的合成：合成了ER伴侣钙连接蛋白和钙网蛋白的拟定配体结构。研究了特异性相互作用的分析。合成了推测参与EDEM/Htm 1 p识别的八氨基糖基化聚糖.高效合成糖肽的方法研究开发了寡糖-天冬酰胺键的构建、硫酯选择性肽键形成和固相肽延伸的新方法. C-甘露糖基色氨酸（CMW）及其衍生物的合成：合成了各种类型的含CMW的糖肽，以及CMW的葡萄糖类似物.低聚糖的简易合成方法：开发了新型的连接体、实时监测聚合物支持的低聚糖合成的方法以及捕获释放纯化方法.酶抑制剂的合成：系统地合成了双底物型唾液酸转移酶衍生物，并对其活性进行了检测。

The aim of this study was to develop methodologies for the synthesis of glycoprotein glycans and related molecular probes. The following results were obtained.1. Synthesis of asparagines-linked glycoprotein glycans: Proposed ligand structure of ER chaperones calnexin and calreticulin was synthesized. Analysis of specific interaction was investigated. Octamarnnrosylated glycans, which are hypothesized to be involved n the recognition of EDEM/Htm1p were synthesized.2. Methodologies for efficient synthesis of glycpeptide Novel methods for the construction of oligosaccharide-asparagine linkage, chenroselctive peptide bond formation using thioester, and peptide elongation on sold support were developed.3. Synthesis of C-mannnosyl tryptophan (CMW) and its derivatives: Various types of CMW-containing glycopeptides, as well as glucose analogue of CMW were synthesized.4. Methods for the facile synthesis of oligosaccharide: New types of linkers, methods for the real-time monitoring of polymer-support oligosacharide synthesis, and capture release purification methods were developed.5. Synthesis of enzyme inhibitors: Bisubstrate-type derivatives of sialyltransferases were synthesized systematically, and their activities were examined.