Development of new functional glycans and the applications

新型功能聚糖的开发及应用

• 批准号: 05660386
• 负责人: KISO Makoto
• 金额: $ 1.41万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05660386/
• 关键词: sialyl-Lewis X; selectin; cell adhesion; sulpho-Lewis X; immunosuppression; ganglioside; sialic acid; シアリルルイスXガングリオシド; セレクチン-ファミリー; 機能性糖鎖; 抗炎症剤; 細胞接着; 機能性オリゴ糖鎖; シアリルLe^Xガングリオシド; ガングリオシドGM_4; 1-デオキシノジリマイシン

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.

我们通过使用各种合成碳水化合物类似物对Selectin识别的分子需求进行了对siAllyl-Lewis X的特定修饰，这是白细胞 - 内皮细胞粘附分子的结合表位（Selectins）。 E-和L-选择蛋白需要在L-纤维糖部分的C-2,3和4处OH组，而P-选择蛋白仅需要OH-3。除羧基外，唾液酸部分的修饰对任何选择素的结合几乎没有影响。所有三个选择素结合的都可以有效地与硫酸糖类似物有效地结合，其中唾液酸和神经酰胺分别被硫酸盐基团和人造长链烷基（B-30）代替。现在，正在研究该分子的生物医学应用，作为一种抗炎和抗中移位剂。这是一种合成的2-（四甲基）六烷基0-（5-乙酰胺-3,5,5-3,5-二氧氧基-D-didoxy-d-didoxy-d-didoxy-d-didoxy-d----甘油 - alpha-alpha-alpha-alpha-alpha-d-galacto-2-甲状腺酸 - 2-----甲状腺酸 - 2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2-2 -0-beta-d-d-galactopypyranosyl-（1-4）-beta-d-d-葡萄糖苷，一种神经节GM3的类似物，显着抑制了细胞免疫反应。该作用在定量上与环孢菌素A的作用相似。

项目成果

M.Yoshida: "Synthesis of chemically modified sialic acid-containing sialyl-Lewis X ganglioside analogues recognized by the selectin family" Glycoconjugate J.10. 3-15 (1993)

M.Yoshida：“选择素家族识别的化学修饰的含唾液酸的唾液酸-Lewis X 神经节苷脂类似物的合成”Glycoconjugate J.10。

Hasegawa.A.& Kiso, M.: "Synthesis of sialyl Lewis X ganglioside and analogs. in Neoglycolipids." Methods in Enzymol.242. 158-173 (1994)

长谷川.A.

C.-T.Yuen: "Sulfated blood group Lewis A.A superior oligosaccharide ligand for human E-selectin" J.Biol.Chem.269. 1595-1598 (1994)

C.-T.Yuen：“硫酸化血型 Lewis A.A 人 E-选择素的优质寡糖配体”J.Biol.Chem.269。

A. Kameyama: "Total synthesis of tumor-associated ganglioside, sialyl Lewis A" J. Carbohydr. Chem.13. 641-654 (1994)

A. Kameyama：“肿瘤相关神经节苷脂，唾液酸路易斯 A 的全合成”J. CarboHydr。

Kiso, M., Furui, H., Ando, K.& Hasegawa, A.: "Synthesis of 1-deoxynojirimycin-containing oligosaccharides related to the cancer-associated sialyl-Lewis A antigen recognized by LEC-CAMs (Selectins) ." J.Carbohydr. Chem.12. 673-677 (1993)

木曾 M.、古井 H.、安藤 K.