1994 Fiscal Year Final Research Report Summary
Development of new functional glycans and the applications
Project/Area Number |
05660386
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Research Category |
Grant-in-Aid for General Scientific Research (C)
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Allocation Type | Single-year Grants |
Research Field |
Applied molecular and cellular biology
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Research Institution | Gifu University |
Principal Investigator |
KISO Makoto Gifu University, Professor, 農学部, 教授 (90092931)
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Co-Investigator(Kenkyū-buntansha) |
HASEGAWA Akira Gifu University, Professor, 農学部, 教授 (10026429)
ISHIDA Hideharu Gifu University, Assoc.Prof., 農学部, 助教授 (20203002)
|
Project Period (FY) |
1993 – 1994
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Keywords | sialyl-Lewis X / selectin / cell adhesion / sulpho-Lewis X / immunosuppression / ganglioside / sialic acid |
Research Abstract |
We have examined the molecular requirements of selectin recognition by use of a variety of synthetic carbohydrate analogues with specific modifications on the sialyl-Lewis X,a binding epitope of leukocyte-endothelial cell adhesion molecules (selectins). E- and L-Selectins require OH groups at c-2,3 and 4 of the L-fucose moiety, while p-selectin requires only oh-3. Modifications of the sialic acid moiety, except for the carboxyl group, have little effect on the binding of any of the selectins. All three selectins-bound efficiently to an sulpho-Lewis X analogue in which sialic acid and ceramide are replaced with the sulfate group and an artificial long-chain alkyl (B-30) , respectively. This molecule is now being examined for biomedical applications as an anti-inflammatory as well as anti-metastatic agent. It is of interest that a synthetic 2- (tetradecyl) hexadecyl 0- (5-acetamido-3,5-didoxy-D-glycero-alpha-D-galacto-2-nonulopyranosylonic acid) - (2-3) -0-beta-D-galactopyranosyl- (1-4) -beta-D-glucopyranoside, an analogue of ganglioside GM3, markedly inhibited the cellular immune response. This effect was quantitatively similar to that of cyclosporin A.
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[Publications] Brandley, B.K., Kiso, M., Abbas, S., Nikrad, P., Srivastawa, O., Foxall, C,Oda, Y.& Hasegawa, A.: "Structure-function studies on selectin carbohydrate ligands. Modification to fucose, sialic acid and sulphate as a sialic acid replacement." Glycobiology. 3. 633-639 (1993)
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「研究成果報告書概要(欧文)」より
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[Publications] Kiso, M., Furui, H., Ando, K., Ishida, H.& Hasegawa, A.: "Systematic synthesis of N-methyl-1-deoxynojirimycin-containing Lex, Lea, sialyl-Lex and sialyl-Leaepitopes recognized by selectins." Bioorganic & Medicinal Chemistry. 2. 1295-1308 (1994)
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[Publications] Yuen, C.-T., O'Brien, J., Stoll, M., Lemonie, R., Lubineau, A., Kiso, M., Hasegawa, A., Nicolaou, K., & Feizi, T.: "Sulfated blood group Lewis A.A superior oligosaccharide ligand for human E-selectin." J.Biol. Chem.269. 1595-1598 (1994)
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「研究成果報告書概要(欧文)」より
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