| Project/Area Number |
59870071
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | School of Pharmaceutical Sciences, Kitasato University |
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Principal Investigator |
OGURA Haruo School of Pharmaceutical Sciences, Kitasato University, 薬学部, 教授 (90050335)
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| Co-Investigator(Kenkyū-buntansha) |
OSAWA Toshiaki Faculty of Pharmaceutical Sciences, University of Tokyo, 薬学部, 教授 (40012603)
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| Project Period (FY) |
1984 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥4,600,000 (Direct Cost: ¥4,600,000)
Fiscal Year 1986: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1985: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1984: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | sialic acid / N-acetylneuraminic acid / 2-deoxyneuraminic acid / mucin analog / sialyllactose / cholesterol glycoside / rate of hydrolysis reaction / metabolism of sialic acid / sialyltransferase inhibition / 癌転移阻害剤 / 免疫調節 / 癌細胞 / 細胞障害活性 / 癌転移抑制効果 |
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| Research Abstract |
Sialic acid as constituents of glycoproteins, glycolipids, and oligosaccharides plays an important role in many animal cells. N-Acetylneuraminic acid the most important sialic acid was crystallized to different forms, and the anomeric configuration of both crystls was confirmed as the <beta> -configuration. Syntheses of various kind of sialic acid derivatives - mucin analogs, sialyllactose, monosaccharide and disaccharide nucleoside analogs - were prepared from methyl 2-chloro-N-acetyl-4,7,8,9-tetra-O-acetyl- <beta> -D-neuraminate.
Confirmation of the stereochemistry of these derivatives was performed by means of NMR and CD spectral determination. Hydrolysis experiment of the glycosidic bond by HPLC was also useful method for confirmation of anomeric stereochemistry.
Sialic acid derivatives show proliferal and immunological functions of murine lymphocyte. Especially, 5-fluoro-2',3'-O-isopropylidene (KI-8110) and 2',3'-di-O-acetylinosine (KI-8115) derivatives were most effective owing to the inhibition of sialyltransferase on the lymphocyte surface.KI-8110 inhibited the transfer of sialic acid to its endogenous acceptor in NL-17 and NL-44 cells, and inhibited the metastasis to the lung.
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