Project/Area Number |
12306007
|
Research Category |
Grant-in-Aid for Scientific Research (A)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Bioproduction chemistry/Bioorganic chemistry
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Research Institution | Gifu University |
Principal Investigator |
KISO Makoto Gifu University, Agriculture, Professor, 農学部, 教授 (90092931)
|
Co-Investigator(Kenkyū-buntansha) |
ANDO Susumu Tokyo Metropolitan Institute of Gerontology, Biomembrane, Vice-president, 生体膜部門, 副所長(研究職) (30073000)
KANNNAGI Reiji Aichi Cancer Center, Pathology, Director, 病理学第二部, 部長(研究職) (80161389)
ISHIDA Hideharu Gifu University, Agriculture, Associate Professor, 農学部, 助教授 (20203002)
|
Project Period (FY) |
2000 – 2003
|
Project Status |
Completed (Fiscal Year 2003)
|
Budget Amount *help |
¥34,500,000 (Direct Cost: ¥30,000,000、Indirect Cost: ¥4,500,000)
Fiscal Year 2003: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2002: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2001: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
Fiscal Year 2000: ¥15,000,000 (Direct Cost: ¥15,000,000)
|
Keywords | selectin / ganglioside / sialic acid / sialyl Lewis X / sialyl Lewis A / siglec / CD38 / glycolipids / シアロ糖鎖 / シアリル ルイスメ / O-グリコシド型糖鎖 / フコシルトランスフェラーゼ / α-シリーズガングリオシド |
Research Abstract |
[1]Systematic synthesis of newly discovered sulfated sialyl Lewis X variants and elucidation of a novel immunity regulation system : It has been demonstrated at the molecular level, for the first time, that the de-N-acetylation of sialic acid (activation) and lactamization (inactivation) are the key reactions in the L-selectin ligand processing by the systematic precise synthesis (Carbohydr.Res.,338,2793-2812,2003). Thus, the highly efficient total synthesis of sialyl 6-O-sulfo Lewis X hexasaccharide gangliosides and sialyl 6-O-sulfo paraglobosides containing the de-N-acetylated and lactamized sialic acids have successfully carried out. By using the ~ synthesized ganglioside probes, the lactamized-sialyl 6-O-sulfo Lewis X was identified to be a major determinant recognized by G159 monoclonal antibody. [2]A novel sulfated ganglioside GSC-338 designed from α-series hybrid-type ganglioside has been found to be a super-high affinity ligand of myelin-associated glycoprotein (MAG), a neural siglec 4a (Carbohydr.Res.,338,1621-1639,2003). It has also been found that GSC-338 is a potent inhibitor of CD38 NADase expressed on leukocytes (Bioorg.Med.Chem.Lett.,13,3441-3445,2003). [3]The first total synthesis of α-(2-3)/α(2-6)-disialyl lactotetraosyl ceramide and disialyl Lewis X ganglioside as cancer-associated carbohydrate antigents has been carried out (Carbohydr. Res.,338,503-514,2003). The biosynthetic route and the expected functions were elucidated at the molecular level (J.Biol.Chem.,278,22787-22794,2003)
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