Synthesis and Function of Modified Oligosaccharides

改性低聚糖的合成与功能

• 批准号: 06453212
• 负责人: HASHIMOTO Hironobu
• 金额: $ 4.61万
• 依托单位: Tokyo Institute of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06453212/
• 关键词: 5-Thioaldose; Fucosidase; Inhibitor; Fucosyltransferase; Sialyltransferase; Pseudooligosaccharide; Galactosyltransferase; Glycosyltransferase; CMP-シアル酸輸送タンパク; 修飾オリゴ糖; グリコシダーゼ; グリコシルトランスフェラーゼ; アザ糖; 阻害剤

In order to elucidate the reaction machanisms of glucosidases and glycosyltransferases, various oligosaccharide mimics were synthesized and their biochemical behaviors were examined. Di-and trisaccharides having 5-thio-L-fucose residue at the non-reducing end were synthesized and the former analogs were proved to be effective as a linkage-specific inhibitor against alpha-L-fucosidase, while one (H type 2) of the latter analogs showed different behaviors from the natural trisaccharide toward the lectin and antibody. Further, synthetic routes of disaccharides having azasugar at the non-reducing end through amidine linkage were developed. Various glycosyl donor analogs of glycosyltransferases were synthesized. Among them, UDP-5-thio-GalNAc, GDP-5-thio-L-Fuc, and sialyl phosphonate analog of CMP-NeuNAc were found to be active as glycosyl donors, for beta-1,4-galactosyltransferase, alpha-L-fucosyltransferase, and alpha-sialytransferase, respectively.

为了阐明葡萄糖苷酶和糖基转移酶的反应机理，合成了各种寡糖模拟物，并研究了它们的生化行为。合成了在非还原末端具有5-硫代-L-岩藻糖残基的二-和三糖，并且前一个类似物被证明是有效的作为针对α-L-岩藻糖苷酶的连接特异性抑制剂，而后一个类似物（H型2）显示出与天然三糖不同的对凝集素和抗体的行为。此外，还开发了通过脒键在非还原端具有氮杂糖的二糖的合成路线。合成了糖基转移酶的各种糖基供体类似物。其中，发现UDP-5-硫代-GalNAc、GDP-5-硫代-L-Fuc和CMP-NeuNAc的唾液酸膦酸酯类似物分别作为β-1，4-半乳糖基转移酶、α-L-岩藻糖基转移酶和α-唾液酸转移酶的糖基供体具有活性。

项目成果

M.Izumi: "Synthesis of 5-Thio-L-fucose-Containing Disaccharides,as Sequence-Specific Inhibitors,and 2'Fucosyllactose,as a Substrate of α-L-Fucosidases." J.0rg.Chem.62. 992-998 (1997)

M.Izumi：“作为序列特异性抑制剂的 5-硫代-L-岩藻糖和作为 α-L-岩藻糖苷酶底物的 2岩藻糖的合成”J.0rg.Chem.62-。 998 (1997)

Hironobu HASHIMOTO,Tsuyoshi ENDO,and Yasuhiro KAJIYAMA: "Synthesis of the First Tricomponent Bisubstrate Analogue That Exhibits Potent Inhibition against GlcNAc : beta-1,4-Galactosyltransferase." J.Org.Chem.62. 1914-1915 (1997)

Hironobu HASHIMOTO、Tsuyoshi ENDO 和 Yasuhiro KAJIYAMA：“第一个对 GlcNAc 具有有效抑制作用的三组分双底物类似物的合成：β-1,4-半乳糖基转移酶。”

M.Izumi: "A Facile synthesis of 5-thio-L-fucose and 5-thio-D-arabinose from D-arabinose" Carbohydr.Res.280. 287-302 (1996)

M.Izumi：“从 D-阿拉伯糖轻松合成 5-硫代-L-岩藻糖和 5-硫代-D-阿拉伯糖”CarboHydr.Res.280。

M.Izumi: "A Facile Synthesis of 5-Thio-L-fucose and 5-Thio-D-arabinose from D-Arabinose." Carbohydr.Res.280. 287-302 (1996)

M.Izumi：“从 D-阿拉伯糖轻松合成 5-硫代-L-岩藻糖和 5-硫代-D-阿拉伯糖。”

Masayuki IZUMI,Osamu TSURUTA,Satoru HARAYAMA,and Hironobu HASHIMOTO: "Synthesis of 5-Thio-L-fucose-Containing Disaccharides, as Sequence-Specific Inhibitors, and 2'-Fucosyllactose, as a Substrate of alpha-L-Fucosidases." J.Org.Chem.62. 992-998 (1997)

Masayuki IZUMI、Osamu TSURUTA、Satoru HARAYAMA 和 Hironobu HASHIMOTO：“合成 5-硫代-L-岩藻糖二糖（作为序列特异性抑制剂）和 2-岩藻糖基乳糖（作为 α-L-岩藻糖苷酶的底物）。”