| Project/Area Number |
12680603
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | Hirosaki University |
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Principal Investigator |
TAKAGAKI Keiichi Hirosaki University, School of Medicine, Biochemistry, Professor, 医学部, 教授 (70163160)
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| Co-Investigator(Kenkyū-buntansha) |
KAKIZAKI Ikuko Hirosaki University, School of Medicine, Biochemistry, Research Associate, 医学部, 助手 (80302024)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Glycosaminoglycan / Oligosaccharide / Hyaluronidase / オリゴ糖ライブラリー / プロテオグリカン / デコリン / コンドロイチン硫酸E / 精巣性ヒアルロニダーゼ / 糖転移 / デルマタン硫酸 |
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| Research Abstract |
Glycosaminoglycan(GAG) has many kinds of structural domains, which is known to participate in physiological functions such as anticoagulation and antithrombotic activities. It is important to prepare GAG oligosaccharides as investigation models in order to analyze their relationship between structure and function. In this study, I developed the methods of synthesis for the reconstruction of chondroitin sulfate oligosaccharides using testicular hyaluronidase, which is an endo-β-N-acetylhexosaminidase. The reaction occurs with changing combinations of chondroitin(Ch), chondrortin 4-sulfate(Ch4S), chondroitin 6-sulfate(Ch6S) and the other GAGs as an acceptor and a donor of transglycosylation, which reconstructs the sugar chain. Thus, it was possible to custom-synthesize oligosaccharides by controlling their combinations. Therefore, it was possible to prepare many libraries of chondroitin sulfate oligosaccharides including chimeric unnatural GAGs. The application of the oligosaccharides library produced by the recombination technology was done as follows.
We found that chondroitin sulfate E(ChS-E) has the specific affinity for type V collagen. The oligosaccharide obtained by hydrolysis of ChS-E using testicular hyaluronidase combined with the new sugar residue from the reconstruction of the sugar chain and essential structure of the specific affinity in the ChS-E side of the synthesized sugar chain with a specific arrangement was examined. As a result, it was known that GlcAβ1-3GaINAc(4S,6S) structure which exists at the nonreducing terminal of the oligosaccharide was important. We expect that these libraries will contribute to new developments of glycotechnology in the future.
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