Development of Sialic Acid Related Compounds to Immunological Regulator

唾液酸相关化合物免疫调节剂的开发

• 批准号: 59870071
• 负责人: OGURA Haruo
• 金额: $ 2.94万
• 依托单位: School of Pharmaceutical Sciences, Kitasato University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Developmental Scientific Research
• 财政年份: 1984
• 资助国家: 日本
• 起止时间: 1984 至 1986
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-59870071/
• 关键词: 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

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.

唾液酸作为糖蛋白、糖脂和寡糖的成分，在许多动物细胞中发挥着重要作用。 N-乙酰神经氨酸(最重要的唾液酸)被结晶成不同的形式，并且两种晶体的异头构型均被证实为β-构型。由甲基2-氯-N-乙酰基-4,7,8,9-四-O-乙酰基-β-D-神经氨酸酯合成了各种唾液酸衍生物——粘蛋白类似物、唾液酸乳糖、单糖和二糖核苷类似物。通过NMR确认了这些衍生物的立体化学 和 CD 光谱测定。 HPLC 糖苷键水解实验也是确认异头立体化学的有用方法。唾液酸衍生物具有小鼠淋巴细胞的增殖和免疫功能。特别是，5-氟-2',3'-O-异丙叉 (KI-8110) 和 2',3'-二-O-乙酰肌苷 (KI-8115) 衍生物由于抑制淋巴细胞表面的唾液酸转移酶而最有效。KI-8110 抑制唾液酸向 NL-17 和 NL-44 中的内源受体转移 细胞，并抑制肺转移。

项目成果

小倉治夫: ファインケミカル. 15. 5-11 (1986)

小仓春夫：精细化学品。15. 5-11 (1986)

Haruo OGURA et al.: "Syntheses of Sialic Acid Derivatives" YUKIGOUSEIKAGAKU KYOKAISHI. 42. 536-543 (1984)

Haruo OGURA 等：“唾液酸衍生物的合成”YUKIGOUSEIKAGAKU KYOKAISHI。

I.Kijima-Suda;S.Toyoshima;M.Itoh;K.Furuhata;H.Ogura;T.Osawa: Chem.Pharm.Bull.

I.Kijima-Suda；S.Toyoshima；M.Itoh；K.Furuhata；H.Ogura；T.Osawa：Chem.Pharm.Bull。

Isao SUDA et al.: "Mechanism of Metastasis" NIHON RINSHO. 44. 367-375 (1986)

Isao SUDA 等：“转移的机制”NIHON RINSHO。

豊島聰,大澤利昭: Oncologia. 13. 13-24 (1985)

Satoshi Toyoshima，Toshiaki Osawa：《肿瘤学》13. 13-24 (1985)。