Development of Sialic Acid Related Compounds to Immunological Regulator

唾液酸作为糖蛋白、糖脂和低聚糖的组成成分，在许多动物细胞中起着重要作用。最重要的唾液酸n -乙酰神经氨酸结晶成不同的形态，两种晶体均为< β > -构型。以甲基2-氯-n -乙酰-4,7,8,9-四- o-乙酰- < β - > - d -神经胺酸为原料，合成了各种唾液酸衍生物粘蛋白类似物、唾液乳糖、单糖和双糖核苷类似物。这些衍生物的立体化学性质通过核磁共振和CD光谱测定进行了证实。用高效液相色谱法对糖苷键进行水解实验，也是确证其异构立体化学性质的有效方法。唾液酸衍生物对小鼠淋巴细胞具有增殖和免疫功能。特别是5-氟-2′，3′- o-异丙烯（KI-8110）和2′，3′-二- o-乙酰氨基赖氨酸（KI-8115）衍生物由于抑制淋巴细胞表面的唾液基转移酶而最有效。KI-8110抑制NL-17和NL-44细胞唾液酸向其内源性受体转移，并抑制其向肺转移。

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.