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Glycotechnological development of a drug derived from urinastatin for the inhibition of premature delivery

Research Project

Project/Area Number 26462470
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionHirosaki University

Principal Investigator

Kakizaki Ikuko  弘前大学, 医学研究科, 准教授 (80302024)

Co-Investigator(Kenkyū-buntansha) 田中 幹二  弘前大学, 医学部附属病院, 准教授 (20311540)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsウリナスタチン / ヒアルロン酸 / プロテオグリカン / 糖鎖工学 / 早産
Outline of Final Research Achievements

The chondroitin sulfate chain of urinastatin, which is used as an anti-inflammatory medicine to inhibit premature delivery, was remodeled to hyaluronan to create hyaluronan hybrid urinastatin. Hyaluronan hybrid urinastatin inhibited protease (trypsin, plasmine, and elastase) and glycosidase (hyaluronidase) activity. Inhibition of the hyaluronan hybrid urinastatin toward the enzymes was similar though slightly weaker than the native urinastatin but stronger than the urinastatin without chondroitin sulfate chain nor hyaluronan, indicating the importance of the glycosaminoglycan chain and its sulfation. Further, experiments using cultured uterine cells showed that anti-inflammatory effects of the hyaluronan hybrid urinastatin were also similar to the native urinastatin. However, attractive interaction between hyaluronan hybrid urinastatin and phospholipid, abundant in the outer layer of the plasma membrane, was stronger than that of native urinastatin.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (6 results)

All 2015 2014 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Acknowledgement Compliant: 3 results,  Open Access: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Journal Article] Enzymatic synthesis of hyaluronan hybrid urinary trypsin inhibitor.2015

    • Author(s)
      Kakizaki, I., Takahashi, R., Yanagisawa, M, Yoshida, F, and Takagaki, K.
    • Journal Title

      Carbohydr Res.

      Volume: 413 Pages: 129-134

    • DOI

      10.1016/j.carres.2015.05.009

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Characterization of Proteoglycan and Hyaluronan in Water-based Delipidated Powder of Salmon Cartilage2015

    • Author(s)
      Kakizaki I., Miura, A., Ito, S., Mineta, T., Hong, J.S., and Kato, Y.
    • Journal Title

      Journal of Applied Glycoscience

      Volume: 62 Issue: 3 Pages: 115-120

    • DOI

      10.5458/jag.jag.JAG-2015_011

    • NAID

      130005094611

    • ISSN
      1344-7882, 1880-7291
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Inhibitory effect of chondroitin sulfate oligosaccharides on bovine testicular hyaluronidase.2015

    • Author(s)
      Kakizaki, I., Koizumi, H., Chen, F., Endo, M.
    • Journal Title

      Carbohydr. Polym.

      Volume: 121 Pages: 362-371

    • DOI

      10.1016/j.carbpol.2014.11.071

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Measurement of intracellular nucleotide sugar levels in hyaluronan-overproducing breast cancer cells.2015

    • Author(s)
      Kakizaki, I., Chanmee, T., Ontong, P., and Itano, N.
    • Organizer
      10th International Conference on Hyaluronan (Hyaluronan 2015)
    • Place of Presentation
      Florence, Italy
    • Year and Date
      2015-06-07
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Enzymatic synthesis of hyaluronan hybrid urinary trypsin inhibitor.2014

    • Author(s)
      Kakizaki, I., Takahashi, R., Yanagisawa, M., Yoshida, T., and Takagaki, K.
    • Organizer
      Hirosaki International Symposium on Transplant 2014
    • Place of Presentation
      Hirosaki, Japan
    • Year and Date
      2014-10-31
    • Related Report
      2014 Research-status Report
  • [Remarks] 弘前大学地域共同研究センター 研究シーズ紹介

    • URL

      http://www.cjr.hirosaki-u.ac.jp/seeds/h26_seeds_1/

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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