Preparation of various xylose derivatives as glycosaminoglycan biosynthesis inhibitor

多种糖胺聚糖生物合成抑制剂木糖衍生物的制备

• 批准号: 23590005
• 负责人: KOKETSU Mamoru
• 金额: $ 3.33万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590005/
• 关键词: グルコサミノグリカン; 阻害剤; キシロース; クリックケミストリー; テトラゾール; トリアゾール; グリコサミノグリカン; 生合成阻害剤; ヘテロ環

This study investigated the development of various GAG biosynthesis inhibitors introducing hydrophobic moieties into xylose.The current study demonstrates that fluoro-xylosides are effective inhibitors of endothelial tube formation in vitro using a matrigel based assay to simulate tumor-associated angiogenesis.In addition, various xylose derivatives were prepared for development of GAG biosynthesis inhibitor. 1,5-Disubstituted-1,2,3-triazole derivatives were synthesized by click chemistry using a ruthenium complex. The reaction of xylose thiourea derivatives with bromide propyne gave 1,3-thiazole derivatives. The reaction with hydrazine gave 1,2,4-triazole derivatives. And the reaction with sodium azide yielded 1,2,3,4-tetrazole derivatives, respectively. Currently, GAG biosynthesis inhibitory ability of these obtained xylose derivatives are carrying out.

本研究通过在木糖中引入疏水基团，开发了多种GAG生物合成抑制剂，并通过基质胶法模拟肿瘤血管生成，证实了氟代木糖苷在体外是有效的血管生成抑制剂。此外，我们还制备了多种木糖衍生物，用于开发GAG生物合成抑制剂。利用钌配合物通过点击化学合成了1，5-二取代-1，2，3-三唑衍生物。木糖硫脲衍生物与溴代丙炔反应生成1，3-噻唑衍生物。与肼反应得到1，2，4-三唑衍生物。与叠氮化钠反应分别得到1，2，3，4-四唑衍生物。目前，正在对这些获得的木糖衍生物的GAG生物合成抑制能力进行研究。

项目成果

Dimerized Glycosaminoglycan Chains Increase FGF Signaling during Zebrafish Development

• DOI: 10.1021/cb400132r
• 发表时间: 2013-05-01
• 期刊: ACS CHEMICAL BIOLOGY
• 影响因子: 4
• 作者: Nguyen, Thao K. N.;Tran, Vy M.;Kuberan, Balagurunathan
• 通讯作者: Kuberan, Balagurunathan