Synthetic studies on the unnatural glycan-linked dolichylpyrophosphates

非天然聚糖连接的多醇焦磷酸酯的合成研究

• 批准号: 11660116
• 负责人: NAKAHARA Yoshiaki
• 金额: $ 1.41万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11660116/
• 关键词: dolichylpyrophosphate; asparagine-linked oligosaccharide; biosynthesis of N-glycan; lipid-intermediate; N-結合型糖鎖

In the biosynthesis of asparagine-linked glycoprotein oligosaccharides, glycan chains grow on a common lipid-intermediate by glycosyltransferases. The chain growing processes have not been well studied because of inaccessibility of the unstable glycosyl dolichylpyrophosphates. There have been a few reports describing the chemical synthesis of N-acetylglucosaminyl, and chitobiosyl dolichylpyrophosphates.On the other hand, we have been interested in the structural requirement of N-glycans in the carbohydrate-mediated biological interactions, In this project, we planned the synthesis of dolichylpyrophosphates carrying oligosaccharides with unnatural glycosidic linkage, which would be the useful probes for the studies of glycan biosynthesis. Before going to the dolichyl pyrophosphate chemistry, the synthetic routes to the N-glycan core pentasaccharides of unnatural structure were investigated. The unnatural α mannoside was derived from the side product of insoluble Ag-mediated mannosylation while α GlcNAc linkage was established using the 2-azidoglucose derivative as a glycosyl donor.The synthesis of the glycosylated dolichylpyrophosphate was next investigated according to the reported synthetic procedures. In order to facilitate monitoring of the reactions especially in the coupling reaction of glycosyl phosphate and dolichyl phosphate, p-toluoyl group was used for the protection of sugar hydroxyl group. The toluoylated intermediates were readily detectable on TLC plates. The GlcNAc-linked dolichylpyrophosphate was synthesized in 20% yield by this method.

在天冬酰胺连接的糖蛋白寡糖的生物合成中，聚糖链在糖基转移酶的常见脂质中间酸中生长。由于不稳定的糖基多环磷酸盐的无法访问，链生长过程尚未得到很好的研究。有一些报道描述了N-乙酰葡萄糖酰基的化学合成，另一方面，我们对N-聚糖的结构需求感兴趣糖苷链接，这将是糖糖生物合成研究的有用问题。在进入Dolichyl焦磷酸化学之前，研究了通往非天然结构N-聚糖核心五糖的合成途径。不自然的α甘露糖苷源自不溶性Ag介导的甘露糖基化的侧产物，而αGlcNAC链接使用2-氮杂葡萄糖衍生物作为糖基供体建立。为了促进对反应的监测，尤其是在糖基磷酸糖基和磷酸二甲基的偶联反应中，使用p-toluoyl组来保护糖羟基。在TLC板上很容易检测到甲氟化的中间体。通过这种方法将GlcNAC连接的多乙基二磷酸二磷酸二磷酸合成20％。

项目成果

H.Hojo, Y.Nakahara: "Recent Progress in the Solid-Phase Synthesis of Glycopeptide"Current Protein and Peptide Science. 1. 43-67 (2000)

H.Hojo，Y.Nakahara：“糖肽固相合成的最新进展”当前蛋白质和肽科学。

Wada, A., et al: "Induction of Human b-Defensin-2 mRNA Expression by Helicobacter pylori in Human Gastric Cell Line MKN45 Cells on cag Pathogenecity Island"Biochem. Biophys. Res. Commun.. 263. 770-774 (1999)

Wada，A.等人：“在cag致病岛的人胃细胞系MKN45细胞中幽门螺杆菌诱导人b-防御素-2 mRNA表达”Biochem。

M.Takatani,T.Nakama,K.Kubo,S.Manabe,Y.Nakahara,Y.Ito,Y.Nakahara: "Synthesis of N-Linked Pentasaccharides with Isomeric Glycosidic Linkage"Glycoconj.J.. 17. 357-370 (2000)

M.Takatani，T.Nakama，K.Kubo，S.Manabe，Y.Nakahara，Y.Ito，Y.Nakahara：“具有异构糖苷键的 N-连接五糖的合成”Glycoconj.J.. 17. 357-370

木曽 眞: "生物化学実験法42 生理活性糖鎖研究法"学会出版センター. 239 (1999)

木曾诚：《生物化学实验方法42种生物活性聚糖研究方法》学会出版中心239（1999）。

H.Hojo,Y.Nakahara: "Recent Progress in the Solid-Phase Synthesis of Glycopeptide"Current Protein and Peptide Science. 1. 43-67 (2000)

H.Hojo，Y.Nakahara：“糖肽固相合成的最新进展”当前蛋白质和肽科学。