Preparation of various xylose derivatives as glycosaminoglycan biosynthesis inhibitor

• Project/Area Number: 23590005
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Chemical pharmacy
• Research Institution: Gifu University
• Principal Investigator: KOKETSU Mamoru 岐阜大学, 工学部, 教授 (50178208)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 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

Research Abstract

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.

Research Products

• [Journal Article] Dimerized Glycosaminoglycan Chains Increase FGF Signaling during Zebrafish Development (2013)
  • Author(s): Thao K. N. Nguyen, Vy M. Tran, Venkataswamy Sorna, Inger Eriksson, Akinori Kojima, Mamoru Koketsu, Duraikkannu Loganathan, Lena Kjellén, Richard I. Dorsky, Chi-Bin Chien, and Balagurunathan Kuberan
  • Journal Title: ACS Chemical Biology Volume: 8 (5) Issue: 5 Pages: 939-948
  • DOI: 10.1021/cb400132r
  • Peer Reviewed
• [Journal Article] Novel glycosaminoglycan biosynthetic inhibitors affect tumor-associated angiogenesis (2011)
  • Author(s): K. Raman, M. Ninomiya, T. K. N. Nguyen, Y. Tsuzuki, M. Koketsu, and B. Kuberan
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 404 Issue: 1 Pages: 86-89
  • DOI: 10.1016/j.bbrc.2010.11.069
  • Peer Reviewed
• [Remarks]
  • URL: http://www1.gifu-u.ac.jp/~ms2/flame_j.htm