Organic Synthesis of Glycoprotein Structural Motifs

这项研究的目的是开发合成糖蛋白多糖和相关分子探针的方法。取得了以下研究成果：1.天冬酰胺连接糖蛋白多糖的合成：合成了内质网伴侣、钙粘蛋白和钙网蛋白的配体结构。对特定的相互作用进行了分析。合成了可能与EDEM/Htm1p识别有关的八氮杂多糖。高效合成糖肽的方法学研究开发了构建寡糖-天冬酰胺键、利用硫代酯形成具有化学选择性的多肽键以及在载体上延伸多肽的新方法。C-甘露醇色氨酸(CMW)及其衍生物的合成：合成了各种含CMW的糖肽，以及CMW的葡萄糖类似物。低聚糖的简便合成方法：开发了新型连接物、聚合物载体低聚糖合成的实时监测方法和捕获释放纯化方法。酶抑制剂的合成：系统地合成了唾液酸基转移酶的双底物类衍生物，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.