| Project/Area Number |
10672090
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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 |
医薬分子機能学
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| Research Institution | The University of Tokushima |
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Principal Investigator |
HORI Hitoshi Faculty of Engineering, The University of Tokushima, Professor, 工学部, 教授 (90119008)
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| Co-Investigator(Kenkyū-buntansha) |
NAGASAWA Hideko Faculty of Engineering, The University of Tokushima, Associate Professor, 工学部, 講師 (90207994)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | α-N-acetyl gahctosamintdase / enzyme inhibitor / imnmnopotentiator / molecular design / anticancer drug / α-N-アセチルガラクトサミニダーゼ / 阻害活性 / 制がん剤分子設計 / がん細胞 |
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| Research Abstract |
It was supposed as one of the mechanisms for immuno-suppression in cancer patients that macrophage activating factor (Gc MAF) could not be produced from a precursor, serum vitamin D-binding protein (Gc protein) due to deglycosylation by a-N-acetyl galactosaminidase (α-NaGalase). It was reported that α-NaGalase increased in cancer patients serum (Yamamoto, N. et al., 1998). To develop a immuno modulator of cancer therapy, the mechanism of immuno-suppression was defined by characterization of α-NaGalase in various tumor cells and α-NaGalase inhibitors was designed and synthesized as immuno potentiator.
1) α-NaGalase activities in tumor cell lysates from Hep G2 and HCT116 cells and normal cell lysates from Chang liver cell and isolated rat hepatocytes were measured. A high specific activity of a-NaGalase was found in tumor cell lines compare to normal cells. Because α-NaGalase deglycosylated exo-type substrate specifically, it was necessary to reinvestigate the deactivation mechanism of GcMAF by a-NaGalase.
2) Azasugar derivatives introduced spィイD12ィエD1 carbon to control a torsional angle between hydroxyl groups were designed and synthesized as a α-NaGalase inhibitor and an immunopotentiator, because a sugar-shaped alkaloid, swainsonine, was a α-mannosidase inhibitor and an immunopotentiator. Their activities of α-NaGalase inhibition and macrophage activation are now under investigation.
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