Syriltes and Biologlacal Enaluativns of Fulkren-Glycosidet.

Syrrites 和 Fulkren-Glycosidet 的 Biologlacal Enaluativns。

• 批准号: 12660096
• 负责人: NISHIDA Yoshihiro
• 金额: $ 1.6万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12660096/
• 关键词: Glycosides; Fullerene; Glycoconjugate; Glycosylation; Glycosyltromsferase; Shiga toxins; Active Oxygen; Fullerenal; フレノール; 生理活性; 糖鎖結合フラーレン; 糖転移酵素; セレクチン; L-糖

In this research project, a new type of glycoconjugates, namely, "fullerene g ycoconjugates ' was designed and developed. The C60 conjugates are composed of biologically active active giycosides introduced onto the surface via an N-glycoside linkage. The different property of the two molecules regarding from both physicchemical and biological aspects is expected to induce a novel class of biologically active compounds.Prior to the synthesis of the'Tullerene glycoconjugates", an efficient glycosylation method was deveioped, which involved the use of new thio-glycosyl donors and galactosyltransferase. The new thio-glycosyl donor was applied conveniently to the formation of globotn- and biosides possessing high biological potential to trap Shiga toxins and deactivate the toxins. A bovine galactosyltransferase was found to catalyse a novel class of enzymic reactions applicable to non-natural L-sugars and acyclic substrates.Several types of biologiclaly active saccharides were coupled with C60 fullerene via thermal couplmg between a glycoylazide and C60. The derived fullerene glycococonjugates as well as fullerenol conjugates were water-miscible and proved to show high biological potential to block carbohydrate-protein binding involved in many biological phenomena.

本课题设计并开发了一种新型的糖缀合物，即“富勒烯糖缀合物”。C60缀合物由具有生物活性的活性糖苷通过n -糖苷键引入表面组成。这两种分子在物理化学和生物学方面的不同性质有望诱导出一类新的生物活性化合物。在合成“tullerene糖缀合物”之前，开发了一种高效的糖基化方法，该方法涉及使用新的硫代糖基供体和半乳糖基转移酶。新的硫代糖基供体可方便地用于形成具有高生物潜力的球状和生物苷，以捕获志贺毒素并使其失活。牛半乳糖转移酶被发现能催化一类新的酶反应，适用于非天然l糖和无环底物。几种具有生物活性的糖类通过糖酰肼与C60之间的热偶联与C60富勒烯偶联。衍生的富勒烯糖缀合物和富勒烯醇缀合物是水混溶的，并被证明具有很高的生物潜力，可以阻断碳水化合物与蛋白质的结合，参与许多生物现象。

项目成果

Y. Nishida, H. Uzawa, T. Toba, K. Sasaki, H.: "A Facile Synthesis ofL- and P-Selectin Blockers via Copolymerization of Vinyl Monomers Constructing the Key Carbohydrate Modules of Sulfated LewisX Mimics"Biomacromolecules.. 1. 68-78 (2000)

Y. Nishida, H. Uzawa, T. Toba, K. Sasaki, H.：“通过乙烯基单体的共聚合轻松合成 L-和 P-选择素阻断剂，构建硫酸化 LewisX 模拟物的关键碳水化合物模块”生物大分子.. 1.

H.Dohi(他3名): "Methylsalicyl β-D-Galactopyranoside, A Non-Maloderous Thio Glycosylation Donor For the Synthesis of Globosyl α(1-4)-Linkages"Synlett.,. NO9. 1446-1448 (2001)

H. Dohi（其他 3 名）：“甲基水杨基 β-D-吡喃半乳糖苷，用于合成球基 α(1-4)-连接的非恶臭硫代糖基化供体”Synlett., 1446-1448。

Y.Nishida (他 3名): "The First Bovine β1,4-Galactosyltransferase Reaction with an Acyclic Accepter Substrate"Org. Lett.. 3. 1-3 (2001)

Y. Nishida（和其他 3 人）：“第一个牛 β1,4-半乳糖基转移酶与无环受体底物的反应”Org. 3. 1-3 (2001)

Y. Nishida, H. Tamakoshi, Y. Kitagawa, K. Kobayashi, J. Thiem: "A Novel Bovine (31,4-Galactosyltransferase Reactions to Yield p-D-Galactosyl(l-3)-linkage with L-Series Sugars Substrates"Angew.Chem.. 112. 2074-2077 (2000)

Y. Nishida、H. Tamakoshi、Y. Kitakawa、K. Kobayashi、J. Thiem：“一种新型牛（31,4-半乳糖基转移酶反应，产生与 L 系列糖底物的 p-D-半乳糖基（l-3）-连接”

A.YASHIRO(他4名): "Beta-Hydroxy Nitrile and beta-Hydroxy Oxime Derivatives of [60]fullerene by Nucleophilic Ring Cleavage of Fulleroisoxazoline and Isoxazolidine in the Presence of Methanol"Synlett. 361-362 (2000)

A. YASHIRO（其他 4 名）：“在甲醇存在下通过富勒异恶唑啉和异恶唑烷的亲核环裂解得到[60]富勒烯的β-羟基腈和β-羟基肟衍生物”Synlett 361-362 (2000)。