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Drug discovery of innovative small molecules with inhibition of RAGE-GAG interaction

Research Project

Project/Area Number 25670018
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Biological pharmacy
Research InstitutionHokkaido University

Principal Investigator

KAZUYUKI Sugahara  北海道大学, 先端生命科学研究科(研究院), 名誉教授 (60154449)

Co-Investigator(Kenkyū-buntansha) MIZUMOTO Shuji  名城大学, 薬学部, 助教 (40443973)
Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordsコンドロイチン硫酸 / RAGE / プロテオグリカン / 癌 / 糖鎖創薬 / 低分子化合物 / 転移 / アルツハイマー病 / 老化 / ヘパラン硫酸 / 糖尿病 / オリゴ糖
Outline of Final Research Achievements

Previously, we demonstrated that pulmonary metastasis is initiated by interaction of CS chain on tumor cells with Receptor for Advanced Glycation End-products (RAGE) on lung. The aim of this study was to develop the seeds of new drugs, oligosaccharides, and small molecular compounds. It was established the preparation of oligosaccharides by the hydrolysis of CS-E with a subcritical water microreaction system, and the screening methodology for effective oligosaccharides by inhibition of the interaction of CS-E with RAGE. These observations will provide the seeds of new anti-cancer drug.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (16 results)

All 2015 2014 2013 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results,  Acknowledgement Compliant: 6 results,  Open Access: 2 results) Presentation (9 results) (of which Invited: 2 results)

  • [Journal Article] Cloning and characterization of a novel chondroitin sulfate/dermatan sulfate 4-O-endosulfatase from a marine bacterium.2015

    • Author(s)
      Wenshuang Wang, Wenjun Han, Xingya Cai, Xiaoyu Zheng, Kazuyuki Sugahara, and Fuchuan Li
    • Journal Title

      Journal of Biological Chemistry

      Volume: 290 Issue: 12 Pages: 7823-7832

    • DOI

      10.1074/jbc.m114.629154

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Receptor protein tyrosine phosphatase beta/zeta is a functional binding partner for vascular endothelial growth factor.2015

    • Author(s)
      Marina Koutsioumpa, Evangelia Poimenidi, Evangelia Pantazaka, Christina Theodoropoulou, Angeliki Skoura, Vasileios Megalooikonomou, Nelly Kieffer, Jose Courty, Shuji Mizumoto, Kazuyuki Sugahara, and Evangelia Papadimitriou.
    • Journal Title

      Molecular Cancer

      Volume: 14 Issue: 1 Pages: 19-19

    • DOI

      10.1186/s12943-015-0287-3

    • NAID

      120005906915

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Skeletal dysplasia in a consanguineous clan from the island of Nias/Indonesia is caused by a novel mutation in B3GAT3.2015

    • Author(s)
      Birgit S. Budde, Shuji Mizumoto, Ryo Kogawa, Christian Becker, Janine Altmuller, Holger Thiele, Franz Ruschendorf, Mohammad R. Toliat, Gerrit Kaleschke, Johannes M. Hammerle, Wolffang Hohne, Kazuyuki Sugahara, Peter Nurnberg, Ingo Kennerknecht.
    • Journal Title

      Human Genetics

      Volume: in press Issue: 7 Pages: 691-704

    • DOI

      10.1007/s00439-015-1549-2

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Novel chondroitin sulfate oligosaccharide motifs as biomarkers: insights into their involvement in brain development.2015

    • Author(s)
      Kazuyuki Sugahara
    • Journal Title

      Advances in Experimental Medicine and Biology

      Volume: 842 Pages: 165-183

    • DOI

      10.1007/978-3-319-11280-0_11

    • ISBN
      9783319112794, 9783319112800
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Roles of glycosaminoglycans and glycanmimetics in tumor progression and metastasis2014

    • Author(s)
      Basappa, Kanchugarakoppal S. Rangappa, Kazuyuki Sugahara
    • Journal Title

      Glycoconjugate Journal

      Volume: 31 Issue: 6-7 Pages: 461-467

    • DOI

      10.1007/s10719-014-9551-9

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] A novel eliminase from a marine bacterium that degrades hyaluronan and chondroitin sulfate.2014

    • Author(s)
      Wenjun Han, Wenshuang Wang, Mei Zhao, Kazuyuki Sugahara, and Fuchuan Li
    • Journal Title

      Journal of Biological Chemistry

      Volume: 289 Issue: 40 Pages: 27886-27898

    • DOI

      10.1074/jbc.m114.590752

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Glycosaminoglycans are functional ligands for Receptor for Advanced Glycation End-products (RAGE) in tumors2013

    • Author(s)
      Mizumoto, S., and Sugahara, K.
    • Journal Title

      FEBS Journal

      Volume: 280 Issue: 10 Pages: 2462-2470

    • DOI

      10.1111/febs.12156

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Development of novel monoclonal antibodies against chondroitin sulfate, and their application to glycobiology and glycopathology2014

    • Author(s)
      Peraphan Pothacharoen, Duriya Fongmoon, Shuji Mizumoto, Kazuyuki Sugahara,、Prachya Kongtawelert
    • Organizer
      6th Asian Community of Glycoscience and Glycotechnology (ACGG)
    • Place of Presentation
      University of Hyderabad(インド)
    • Year and Date
      2014-12-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] Effects of Sesamin on the Biosynthesis of Chondroitin Sulfate Proteoglycans in Human Articular Chondrocytes in Primary Culture2014

    • Author(s)
      Peraphan Pothacharoen, Sumet Najarus, Jongkolnee Settakorn, Shuji Mizumoto, Kazuyuki Sugahara, Prachya Kongtawelert
    • Organizer
      Joint Meeting of the Society for Glycobiology and the Japanese Society of Carbohydrate Research
    • Place of Presentation
      Hawai Hotel Hilton(米国)
    • Year and Date
      2014-11-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Effects of Sesamin on the Biosynthesis of Chondroitin Sulfate Proteoglycans in Human Articular Chondrocytes in Primary Culture2014

    • Author(s)
      Peraphan Pothacharoen, Sumet Najarus, Jongkolnee Settakorn, Shuji Mizumoto, Kazuyuki Sugahara, Prachya Kongtawelert
    • Organizer
      Gordon Conference on Proteoglycans
    • Place of Presentation
      Proctor Academy(米国)
    • Year and Date
      2014-07-07
    • Related Report
      2014 Annual Research Report
  • [Presentation] Novel Class of Tetrahydropyridine-fused Pyrazoles, Isoxazolines, and HS-Mimetic Small Molecules as Anti-cancer Agents2013

    • Author(s)
      Rangappa KS, Basappa, Mantelingu K, Sadashiva MP, Feng Li, Gautam Sethi, Kazuyuki Sugahara
    • Organizer
      The 14th tetrahedron symposium
    • Place of Presentation
      Millennium Gloucester Hotel London Kensington (オーストリア)
    • Related Report
      2013 Research-status Report
  • [Presentation] Development of novel monoclonal antibodies against chondroitin sulfate, and their application to glycobiology and glycopathology2013

    • Author(s)
      Peraphan Pothacharoen, Duriya Fongmoon, Shuji Mizumoto, Kazuyuki Sugahara,Prachya Kongtawlert
    • Organizer
      The 5th annual conference for Asian Communications of Glycobiology and Glycotechnology
    • Place of Presentation
      Khon Kaen University(タイ国)
    • Related Report
      2013 Research-status Report
  • [Presentation] Mass preparation of oligosaccharides with intestinal absorption capacity by hydrolysis of chondroitin sulfate polysaccharides with subcritical water microreaction system

    • Author(s)
      Kazuyuki Sugahara, Shuhei Yamada, Shuji Mizumoto, Keiichiro Matsushima, Haruo Ura, Nobuyuki Miyamoto
    • Organizer
      he 13th International Conference on Functional and Medical Foods with Bioactive Compounds
    • Place of Presentation
      The Kyoto Prefectural University of Medicine(京都)
    • Related Report
      2013 Research-status Report
  • [Presentation] Receptor for Advanced Glycation End-products (RAGE) Functions as Receptor for Sulfated Glycosaminoglycans (GAGs): Anti-RAGE Antibody or Sulfated GAGs Inhibit Lung Metastasis of Tumor Cells

    • Author(s)
      Kazuyuki SUGAHARA, Jun TAKAHASHI, Shuji MIZUMOTO
    • Organizer
      22nd International Symposium on Glycoconjugates
    • Place of Presentation
      Dalian Institute of Chemical Phisics, Chinese Academy of Sciences(中国)
    • Related Report
      2013 Research-status Report
  • [Presentation] Wobble chondroitin sulfate oligosaccharide motifs and mass production of oligosaccharides

    • Author(s)
      Kazuyuki Sugahara
    • Organizer
      The 21st Symposium on Glycosaminoglycans
    • Place of Presentation
      Loveno, Lake Como(イタリア)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] Mechanism of glycosaminoglycan-mediated tumor metastasis

    • Author(s)
      Kazuyuki Sugahara and Shuji Mizumoto
    • Organizer
      The 27th International Carbohydrate Symposium
    • Place of Presentation
      Indial Institute of Science(インド)
    • Related Report
      2013 Research-status Report
    • Invited

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Published: 2014-07-25   Modified: 2019-07-29  

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