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Development of a fundamental technology, which is applicable to drug development and therapeutic applications through analysis of sulfated glycosaminoglycan chains

Research Project

Project/Area Number 16390026
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionKOBE PHARMACEUTICAL UNIVERSITY

Principal Investigator

SUGAHARA Kazuyuki  Kobe Pharmaceutical University, Dept.of Biochemistry, Professor, 薬学部, 教授 (60154449)

Co-Investigator(Kenkyū-buntansha) KITAGAWA Hiroshi  Kobe Pharmaceutical University, Dept.of Biochemistry, Professor, 薬学部, 教授 (40221915)
YAMADA Shuhei  Kobe Pharmaceutical University, Dept.of Biochemistry, Assistant Professor, 薬学部, 講師 (70240017)
MIKAMI Tadahisa  Kobe Pharmaceutical University, Dept.of Biochemistry, Assistant Professor, 薬学部, 講師 (20033425)
ASANO Masahide  Kanazawa University, Advanced Science Research Center, Professor, 学際科学実験センター, 教授 (50251450)
三上 雅久  神戸薬科大学, 薬学部, 助手 (20330425)
BAO Xingfeng  神戸薬科大学, 薬学部, 外国人特別研究員
LI Fuchuan  神戸薬科大学, 薬学部, 外国人特別研究員
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2005: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2004: ¥7,700,000 (Direct Cost: ¥7,700,000)
Keywordschondroitin sulfate / dermatan sulfate / sulfotransferase / spondyloepiphysial dysplasia / chondroitin polymerizing factor / RNA intereference / neurite outgrowth / pleiotrpohin / 硫酸基転移酵素 / RNA / 先天性脊椎・骨端異形成症 / RANi / プライオトロフィン
Research Abstract

(1)It has been demonstrated that congenital human spondyloepiphysial dysplasia is caused by a mutation of the chondroitin 6-O-sulfotransferase 1 gene.
(2)The nematode ortholog PAR2.4 of the human chondroitin polymerizing factor (ChPF) that is involved in the biosynthesis of chondroitin has been cloned. Furthermore it was found that downregulation of PAR2.4 by RNAi resulted in the cytokinesis defect during embryonic development of the nematode, which resembled the defect caused by RNAi of chondroitin synthase, indicating the essential role of PAR2.4 in the synthesis of chondroitin as well as the critical role of chondroitin in cytokinesis.
(3)Various biological activities have been demonstrated for CS/DS hybrid chains isolated from shark skin, suggesting a possible therapeutic applications of the CS/DS chains.
(4)It has been proved that the neurite outgrowth promoting activity of CS/DS chains from embryonic mouse brains is exhibited by molecular interactions with a growth factor pleiotrophin. Sulfated decasaccharides derived from the functional domains have also been isolated and sequenced.
(5)A monoclonal antibody specific for dermatan sulfate was developed using an oversulfated dermatan sulfate preparation with a potent neurite outgrowth promoting activity, which was purified from marine ascidian. The antibody apecifically bound to mouse hippocampal neurons, and inhibited the neurite outgrowth promoting activity, which was exhibited by the DS preparation used as an immunogen.
(6)Conventionally herpes simplex virus (HSV-1 and HSV-2) have been considered to infect cells through attachment to heparan sulfate chains on cell surface. In this study it has been demonstrated the infection is more strongly inhibited by CS-E than heparin. Furthermore the CS-E structure has beendemonstrated on cell surface. There results suggest that the viruses use CS-E more efficiently than heparan sulfate for their infection.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (36 results)

All 2006 2005 2004 Other

All Journal Article (20 results) Book (5 results) Patent(Industrial Property Rights) (11 results)

  • [Journal Article] Novel 70 kDa chondroitin sulfate/dermatan sulfate hybrid chains with a unique heterogenoussulfation pattern from shark skin, which exhibit neuritogenic activity and binding activities for growth factors and neurotrophic factors.2005

    • Author(s)
      Chilkunda D. Nandini
    • Journal Title

      J. Biol. Chem. 280(6)

      Pages: 4058-4069

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Heparin-binding growth factor, pleiotrophin, mediates neuritogenic activity of embryonic pig brain-derived chondroitin sulfate/dermatan sulfate hybrid chains.2005

    • Author(s)
      Bao Xingfeng
    • Journal Title

      J. Biol. Chem. 280(10)

      Pages: 9180-9191

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A functional dermatan sulfate epitope containing the iduronate(2-O-sulfate)alpha1-3GalNAc (6-O-sulfate) disaccharide in the mouse brain : DEMONSTRATION USING A NOVEL MONOCLONAL ANTIBODY RAISED AGAINST DERMATAN SULFATE OF ASCIDIAN Ascidia nigra.2005

    • Author(s)
      Bao Xingfeng
    • Journal Title

      J. Biol. Chem. 280(24)

      Pages: 23184-23193

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Chondroitin sulfate characterized by the E disaccharide unit is a potent inhibitor of herpes simplex virus infectivity and provides binding sites for the virus binding to gro2C cells.2005

    • Author(s)
      Bergefall Kicki
    • Journal Title

      J. Biol. Chem. 280(37)

      Pages: 32193-32199

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Demonstration of the Pleiotrophin-binding Oligosaccharide Sequences Isolated from Chondroitin Sulfate/Dermantan Sulfate Hybrid Chains of Embryonic Pig Brains.2005

    • Author(s)
      Bao Xingfeng
    • Journal Title

      J. Biol. Chem. 280(42)

      Pages: 35318-35328

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Novel 70 kDa chondroitin sulfate/dermatan sulfate hybrid chains with a unique heterogenoussulfation pattern from shark skin, which exhibit neuritogenic activity and binding activities for growth factors and neurotrophic factors.2005

    • Author(s)
      Chilkunda D.Nandini et al.
    • Journal Title

      J.Biol.Chem. 280(6)

      Pages: 4058-4069

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Heparin-binding growth factor, pleiotrophin, mediates neuritogenic activity of embryonic pig brain-derived chondroitin sulfate/dermatan sulfate hybrid chains.2005

    • Author(s)
      Bao Xingfeng et al.
    • Journal Title

      J.Biol.Chem. 280(10)

      Pages: 9180-9191

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A functional dermatan sulfate epitope containing the iduronate (2-O-sulfate) alpha1-3GalNAc (6-O-sulfate) disaccharide in the mouse brain : DEMONSTRATION USING A NOVEL MONOCLONAL ANTIBODY RAISED AGAINST DERMATAN SULFATE OF ASCIDIAN Ascidia nigra.2005

    • Author(s)
      Bao Xingfeng et al.
    • Journal Title

      J.Biol.Chem. 280(24)

      Pages: 23184-23193

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Chondroitin sulfate characterized by the E disaccharide unit is a potent inhibitor of herpes simplex virus infectivity and provides binding sites for the virus binding to gro2C cells.2005

    • Author(s)
      Bergefall Kicki et al.
    • Journal Title

      J.Biol.Chem. 280(37)

      Pages: 32193-32199

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Demonstration of the pleiotrophin-binding oligosaccharide sequences isolated from chondroitin sulfate/dermatan sulfate hybrid chains of embryonic pig brains.2005

    • Author(s)
      Bao Xingfeng et al.
    • Journal Title

      J.Biol.Chem. 280(42)

      Pages: 35318-35328

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A functional dermatan sulfate epitope containing the iduronate(2-O-sulfate)alpha1-3GalNAc (6-O-sulfate) disaccharide in the mouse brain : DEMONSTRATION USING A NOVEL MONOCLONAL ANTIBODY RAISED AGAINST DERMATAN SULFATE OF ASCIDIAN Ascidia nigra.2005

    • Author(s)
      Bao Xingfeng
    • Journal Title

      J.Biol.Chem. 280(24)

      Pages: 23184-23193

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Demonstration of the pleiotrophin-binding oligosaccharide sequences isolated from chondroitin sulfate/dermatan sulfate hybrid chains of embryonic pig brains2005

    • Author(s)
      Bao Xingfeng
    • Journal Title

      J.Biol.Chem. 280(42)

      Pages: 35318-35328

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Chondroitin sulfate characterized by the E disaccharide unit is a potent inhibitor of herpes simplex virus infectivity and provides binding sites for the virus binding to gro2C cells2005

    • Author(s)
      Bergefall Kicki
    • Journal Title

      J.Biol.Chem. 280(37)

      Pages: 32193-32199

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Novel 70 kDa chondroitin sulfate/dermatan sulfate hybrid chains with a unique heterogenous sulfation pattern from shark skin, which exhibit neuritogenic activity and binding activities for orowth factors and neurotrophic factors.2005

    • Author(s)
      Chilkunda D.Nandini
    • Journal Title

      J.Biol.Chem. 280(6)

      Pages: 4058-4069

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Heparin-binding growth factor, pleiotrophin, mediates neuritogenic activity of embryonic pig brain-derived chondroitin sulfate/dermatan sulfate hybrid chains.2005

    • Author(s)
      Bao Xingfeng
    • Journal Title

      J.Biol.Chem. 280(10)

      Pages: 9180-9191

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Loss of chondroitin 6-O-sulfotransferase-1 function results in severe human chondrodysplasia with progressive spinal involvement.2004

    • Author(s)
      Thiele, Holger
    • Journal Title

      Proc. Natl. Acad. Sci. USA. 101(27)

      Pages: 10155-10160

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Nematode chondroitin polymerizing factor showing cell/organ-specific expression is indispensable for chondroitin synthesis and embryonic cell division.2004

    • Author(s)
      泉川 友美
    • Journal Title

      J. Biol. Chem. 279(51)

      Pages: 53755-53761

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Loss of chondroitin 6-O-sulfotransferase-1 function results in severe human chondrodysplasia with progressive spinal involvement.2004

    • Author(s)
      Holger Thiele et al.
    • Journal Title

      Proc.Natl.Acad.Sci.USA 101(27)

      Pages: 10155-10160

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Nematode chondroitin polymerizing factor showing cell/organ-specific expression is indispensable for chondroitin synthesis and embryonic cell division.2004

    • Author(s)
      Tomomi Izumikawa et al.
    • Journal Title

      J.Biol.Chem. 279(51)

      Pages: 53755-53761

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Nematode chondroitin polymerizing factor showing cell/organ-specific expression is indispensable for chondroitin synthesis and embryonic cell division.2004

    • Author(s)
      泉川 友美
    • Journal Title

      J.Biol.Chem. 279(51)

      Pages: 53755-53761

    • Related Report
      2004 Annual Research Report
  • [Book] 糖鎖科学の新展開〜機能解明・次世代型材料・医薬品開発に向けて〜2005

    • Author(s)
      三上 雅久
    • Total Pages
      536
    • Publisher
      エヌ・ティ・エス
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 遺伝子医学 MOOK3 糖鎖と病気2005

    • Author(s)
      泉川 友美
    • Total Pages
      291
    • Publisher
      メディカルドゥ
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] タンパク質の翻訳後修飾解析プロトコール2005

    • Author(s)
      山田 修平
    • Total Pages
      286
    • Publisher
      羊土社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 未来を拓く糖鎖科学2005

    • Author(s)
      菅原 一幸
    • Total Pages
      467
    • Publisher
      金芳堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] 蛋白質・核酸・酵素「線虫の細胞分裂を制御する糖鎖コンドロイチン」2004

    • Author(s)
      水口 惣平
    • Total Pages
      96
    • Publisher
      共立出版
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] イカ軟骨のコンドロイチン硫酸E由来の硫酸化八糖、十糖2006

    • Inventor(s)
      菅原一幸
    • Industrial Property Rights Holder
      JST
    • Industrial Property Number
      2006-049308
    • Filing Date
      2006-02-24
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 新規低分子化合物およびその製造方法2006

    • Inventor(s)
      菅原一幸, カンチュガラコッパル, エス・ランガッパ, バサッパ
    • Industrial Property Rights Holder
      JST
    • Industrial Property Number
      2006-081671
    • Filing Date
      2006-03-23
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 糖鎖マーカー認識プローブ、それを用いた神経突起伸長阻害剤、ニューロン染色剤、腫瘍細胞染色剤、免疫組織染色剤、薬学的組成物および2006

    • Inventor(s)
      菅原一幸, Toin van Keppeyelt, Gerdy ten Dam
    • Industrial Property Rights Holder
      JST
    • Industrial Property Number
      2006-084323
    • Filing Date
      2006-03-25
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 新規多糖およびオリゴ糖2006

    • Inventor(s)
      菅原一幸
    • Industrial Property Rights Holder
      菅原 一幸, マルハ株式会社
    • Industrial Property Number
      2006-098722
    • Filing Date
      2006-03-31
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 抗デルマタン硫酸抗体と機能性硫酸化オリゴ糖2006

    • Inventor(s)
      菅原一幸, バオシンフォン
    • Industrial Property Rights Holder
      JST
    • Filing Date
      2006-03-16
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] 抗デルマタン硫酸抗体と機能性硫酸化オリゴ糖2005

    • Inventor(s)
      菅原 一幸, バオ シンフォン
    • Industrial Property Rights Holder
      JST
    • Industrial Property Number
      2005-080724
    • Filing Date
      2005-03-18
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] サメ軟骨のコンドロイチン硫酸由来の硫酸化八糖2005

    • Inventor(s)
      菅原 一幸
    • Industrial Property Rights Holder
      JST
    • Industrial Property Number
      2005-165699
    • Filing Date
      2005
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] プレイオトロフィン結合性および非結合性のコンドロイチン硫酸/デルマタン硫酸オリゴ糖2005

    • Inventor(s)
      菅原一幸, バオ シンフォン
    • Industrial Property Rights Holder
      JST
    • Industrial Property Number
      2005-197587
    • Filing Date
      2005-07-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] プレイオトロフィン結合性および非結合性のコンドロイチン硫酸/デルマタン硫酸オリゴ糖2005

    • Inventor(s)
      菅原一幸, バオシンフォン
    • Industrial Property Rights Holder
      JST
    • Industrial Property Number
      2005-197587
    • Filing Date
      2005-07-06
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] 菅原一幸

    • Inventor(s)
      JST
    • Industrial Property Rights Holder
      PCT/JP2006/305229
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Patent(Industrial Property Rights)] 菅原一幸

    • Inventor(s)
      JST
    • Industrial Property Rights Holder
      特願2006-084337
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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