Development of Glyco-medicines Using Mutant Enzyme of Microbial Endoglycosidase and Establishment of Its Preparation Method
| Project/Area Number |
20380052
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied microbiology
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| Research Institution | Kyoto University |
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Principal Investigator |
YAMAMOTO Kenji Kyoto University, 生物資源環境学部, 客員教授 (70109049)
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| Co-Investigator(Kenkyū-buntansha) |
ASHIDA Hisashi 京都大学, 大学院・生命科学研究科, 准教授 (40379087)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2010: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2009: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2008: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
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| Keywords | エンドグリコシダーゼ / 糖転移活性 / オキサゾリン化合物 / 部位特異的変異酵素 / 化学-酵素合成 / 糖鎖医薬品 / インフルエンザウィルス / 感染阻害剤 / substrate assisted catalysis / サブスタンスP / PAMP12 / リボヌクレアーゼB / シアロ糖鎖 / インフルエンザウイルス / 変異酵素 |
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| Research Abstract |
The endo-β-N-acetylglucosaminidase from Mucor hiemalis isolated from soil sample is unique in that it can transfer en bloc the oligosaccharide of glycoproteins onto different acceptors, and thereby it enzymatically generates diverse glycoconjugates. We performed mutational studies to obtain the mutant of the enzyme which had significantly diminished hydrolysis activity but had a high transglycosylation activity. We have found that some mutant could efficiently exhibit transglycosylation activity using synthetic sugar oxazoline. Therefore, we used the mutant enzyme to synthesize an efficient binding inhibitor for influenza virus, which is composed of sialyloligosaccharides on chitosan. This compound showed sufficient inhibitory activity against influenza virus infection.
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Report
(4 results)
Research Products
(36 results)
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[Journal Article] Efficient Transfer of Sialo-oligosaccharides onto Proteins by Combined Use of a Glycosynthase-like Mutant of Mucor hiemalis Endoglycosidase and Synthetic Sialo-complex-type Sugar Oxazoline.2010
Author(s)
M.Umekawa, T.Higashiyama, Y.Koga, T.Tanaka, M.Noguchi, A.Kobayashi, S.Shoda, W.Huang, L.-X.Wang, H.Ashida, K.Yamamoto
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Journal Title
Biochim. Biophys. Acta 1800
Pages: 1203-1209
NAID
Related Report
Peer Reviewed
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