Organic Synthesis of Glycoprotein Structural Motifs

糖蛋白结构基序的有机合成

• 批准号: 13480191
• 负责人: ITO Yukishige
• 金额: $ 5.12万
• 依托单位: RIKEN(The Institute of Physical and Chmical Resarch)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13480191/
• 关键词: glycoprotein; quality control; chaperone; asparagine-linked; gglycan chain; stereoselctive synthesis; glycopeptide; C-mannosyl tryptophan; 立体選択性; シアル酸; 超高圧; 分子シャペロン; アスパラギン酸フルオリド

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.

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。得到如下结果： 1．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议配体结构。研究了特定相互作用的分析。合成了推测参与EDEM/Htm1p识别的八糖基化聚糖。 2．高效合成糖肽的方法学 开发了构建寡糖-天冬酰胺键、使用硫酯形成陈罗斯选择性肽键以及在固体载体上进行肽延伸的新方法。 3． C-甘露糖基色氨酸(CMW)及其衍生物的合成：合成了各类含CMW的糖肽，以及CMW的葡萄糖类似物。 4．寡糖的简易合成方法：开发了新型连接体、聚合物支撑寡糖合成的实时监测方法以及捕获释放纯化方法。 5．酶抑制剂的合成：系统合成了唾液酸转移酶的双底物型衍生物，并检测了其活性。

项目成果

Kei-ichiro Inamori: "N-acetylglucosaminyltransferase IX acts on the GlcNAcβ1,2-Man α1-Ser/Thr moiety, forming a 2,6-branched structure in brain O-mannosyl glycan"Journal of Biological Chemistry. 279・4. 2337-2340 (2004)

Kei-ichiro Inamori：“N-乙酰氨基葡萄糖转移酶 IX 作用于 GlcNAcβ1,2-Man α1-Ser/Thr 部分，在脑 O-甘露糖基聚糖中形成 2,6 分支结构”《生物化学杂志》279・4。 -2340 (2004)

H.Ando, S.Manabe, Y.Nakahara, Y.Ito: "Solidphase capture-release strategy in soluble polymer support oligosaccharide synthesis"Angew. Chem. Int. Ed.. 40. 4725-4728 (2001)

H.Ando、S.Manabe、Y.Nakahara、Y.Ito：“可溶性聚合物中的固相捕获-释放策略支持寡糖合成”Angew。

E3 ubiquitin ligase that recognizes sugar chains

• DOI: 10.1038/nature00890
• 发表时间: 2002-07-25
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Yoshida, Y;Chiba, T;Tai, T
• 通讯作者: Tai, T

Preparation of sialyl donors carrying functionalized ester substituents : Effects on the selectively of glycosylation

携带官能化酯取代基的唾液酸供体的制备：对糖基化选择性的影响

• 发表时间: 2003
• 期刊: Synlett
• 影响因子: 2
• 作者: A.Ishiwata;Y.Ito
• 通讯作者: Y.Ito

β-Galactosidase-catalyzed intramolecular transglycosylation

β-半乳糖苷酶催化的分子内转糖基化

• 发表时间: 2001
• 期刊: Tetrahedron Lett. 42
• 作者: S.Komba;Y.Ito
• 通讯作者: Y.Ito