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

• Project/Area Number: 26462470
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Hirosaki 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: ¥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.

Research Products

• [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
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Characterization of Proteoglycan and Hyaluronan in Water-based Delipidated Powder of Salmon Cartilage (2015)
  • 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
  • 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
  • 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
  • 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
• [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/