Developmental Research for New Medicines Based on Carbohydrate-cell Recognition

基于糖细胞识别的新药开发研究

• 批准号: 05556019
• 负责人: KISO Makoto
• 金额: $ 4.99万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research (B)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05556019/
• 关键词: 1-deoxynojirimycin; cell adhesion inhibitor; sialyl-Lewis X oligosaccharide; sialyl-Lewis A oligosaccharide; sulfo-Lewis X oligosaccharide; sulfo-Lewis A oligosaccharide; 1-デオキシノジリマイシン; セレクチン結合阻害剤; 糖鎖医薬品; N-アルキル-1-デオキシノジリマイシン; シアリルオリゴサッカライド; シア

We have examined the recognition specificity of sialooligosaccharides by influenza virus and leukocyte cell adhesion molecules (selectin family) at the molecular level. As a results, it has been shown that 1) sialyl paragloboside is one of the best substrate for influenza virus recognition, and 2) both sialyl-Lewis X and sialyl-Lewis A can be well recognized by all selectins. It was also found that sulfo-Lewis X and sulfo-Lewis A function as the selectin ligands with the equal or more afinity than the corresponding sialyl derivatives.Based on these results, a variety of novel oligosaccharides containing 1-deoxynojirimycin have been synthesized as the inhibitors of virus infection and selectin binding. Some of the N-alkyl-1-deoxynojirimycin-containing sialyl-and sulfo-Lewis X and -Lewis A epitope analogs have been found to be potent anti-inflammatory agents by using the animal models. A wide therapeutic application of these compounds is now in progress.

我们在分子水平上研究了流感病毒和白细胞细胞粘附分子（选择素家族）对唾液酸寡糖的识别特异性。结果表明，1) 唾液酸副红细胞糖苷是流感病毒识别的最佳底物之一，2) 唾液酸-Lewis X 和唾液酸-Lewis A 都能被所有选择素很好地识别。还发现磺基-Lewis X和磺基-Lewis A作为选择素配体，其亲和力等于或大于相应的唾液酸衍生物。基于这些结果，合成了多种含有1-脱氧野尻霉素的新型寡糖作为病毒感染和选择素结合的抑制剂。通过使用动物模型，一些含有 N-烷基-1-脱氧野尻霉素的唾液酸基和磺基-Lewis X 和-Lewis A 表位类似物已被发现是有效的抗炎剂。这些化合物的广泛治疗应用正在进行中。

项目成果

Mulligan, M.S., Kiso, M., Hasegawa, A.et al.: "Anti-inflammatory effects of sulphatides in selectin-dependent acute lung injury" International Immunology. 7. 1107-1113 (1995)

Mulligan, M.S.、Kiso, M.、Hasekawa, A.等人：“硫苷脂在选择素依赖性急性肺损伤中的抗炎作用”国际免疫学。

A.Hasegawa: "Synthesis of sialyl and sulfo Lewis X analogs containing a ceramide or 2-(tetradecyl)hexadecyl residue." J. Carbohydr. Chem.14. 353-368 (1995)

A.Hasekawa：“含有神经酰胺或 2-（十四烷基）十六烷基残基的唾液酸基和磺基路易斯 X 类似物的合成。”

S.Ladisch: "Immunosuppressive activity of chemically synthesized ganglioside" Biochemistry. 34. 1197-1202 (1995)

S.Ladisch：“化学合成的神经节苷脂的免疫抑制活性”生物化学。

S.Ladisch: "Immunosuppressive activity of chemically synthesized gangliosides." Biochemistry. 34. 1197-1202 (1995)

S.Ladisch：“化学合成的神经节苷脂的免疫抑制活性。”

木曽 真 他: "ガングリオシド研究法I" 学会出版センター, 259 (1995)

Makoto Kiso 等：《神经节苷脂研究方法 I》学会出版中心，259（1995）