Studies on molecular analysis of cell adhesion mediated by carbohydrate recognitions

碳水化合物识别介导的细胞粘附的分子分析研究

• 批准号: 07456162
• 负责人: KISO Makoto
• 金额: $ 0.32万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07456162/
• 关键词: cell adhesion; selectin family; sialyl Lewis X; sulfo sialyl Lewis X; sialoadhesin family; ganglioside; myelin; スルホ シアリル・ルイスX; 糖鎖リガンド; シアリルLewisX; スルホLewisX; スルファチド; シアロアドヘシン

The selectins are a family of carbohydrate-binding proteins (C-type lectin) involved in leukocyte trafficking, thrombosis, inflammation, tumor metastasis, and so on. In this study, we have demonstrated the mechanism of cell adhesion mediated by selectins not only on the molecular level but also on the level of functional groups by using synthetic sialyl Lewis X and a variety of the analogs. As a result, it has been concluded that : (1) For the binding face of the sialyl Lewis X epitope interacting with E-selectin, the carboxyl group of sialic acid, the 4- and 6-hydroxyls of galactose, and the 2-, 3-, and 4-hydroxyls of fucose are involved in selectin-carbohydrate binding, and further, the fucose moiety is directly involved in the calcium dependency ; (2) Based on the comparison with sulfatide, the roles of carboxyl and sulfate groups, and the presence of the basic amino acids as the counterparts have strongly been suggested ; (3) As the most important finding of the current results, the first total syntheses of the sulfated sialyl Lewis X pentasaccharide gangliosides revealed that the binding of human L-selectin to the 6-0-sulfo (in the GlcNAc moiety) sialyl Lewis X is much stronger than that of sialyl Lewis X,suggesting the possibility of the receptor specificity control by sulfation cappings. In addition, the binding of E-selectin was lost by the 6'-O-sulafation (in the Gal moiety). All these results are the first findings in the world.On the other hand, in a series of studies on clarifying the recognition specificity of sialoadhesin family (I-type lectin), we have demonstrated that ganglioside GQ1balpha is one of the strongest carbohydrate ligands for the binding of myelin-associated glycoprotein (MAG).

选择素是一类糖结合蛋白（C型凝集素）家族，与白细胞运输、血栓形成、炎症、肿瘤转移等有关，本研究利用合成的唾液酸刘易斯X及其类似物，从分子水平和功能基团水平阐明了选择素介导的细胞粘附机制。结果表明：（1）唾液酸刘易斯X表位与E-选择素相互作用的结合面中，唾液酸的羧基、半乳糖的4-和6-羟基以及岩藻糖的2-、3-和4-羟基参与选择素-碳水化合物结合，而且岩藻糖部分直接参与钙依赖性;（2）通过与硫苷脂的比较，提出了羧基和硫酸基的作用以及碱性氨基酸的存在;（3）作为当前结果中最重要的发现，硫酸化唾液酸刘易斯X五糖神经节苷脂的首次全合成揭示了人L-选择素与6-0-磺基（在GlcNAc部分中）sialyl刘易斯X比sialyl刘易斯X强得多，提示通过硫酸化封端控制受体特异性的可能性。此外，E-选择素的结合由于6 '-O-硫酸化（在Gal部分中）而丧失。另一方面，在阐明唾液酸粘附素家族（I型凝集素）识别特异性的一系列研究中，我们证明了神经节苷脂GQ 1balpha是髓鞘相关糖蛋白（MAG）结合的最强糖配体之一。

项目成果

A. Hasegawa: "Carbodrates and Drug Design" Marcel Dekker, Inc., New York(印刷中), (1997)

A. 长谷川：“碳水化合物和药物设计”Marcel Dekker, Inc.，纽约（印刷中），（1997 年）

M.Kiso: "Studies on selectin binding inhibitors : Synthesis of sialyl-LeX and sialyl-LeA epitope analogs containing 2-acetamido derivarive" J.Carbohydr.Chem.15(1). 1-14 (1996)

M.Kiso：“选择素结合抑制剂的研究：含有 2-乙酰氨基衍生物的 sialyl-LeX 和 sialyl-LeA 表位类似物的合成”J.CarboHydr.Chem.15(1)。

M. Kiso: "Studies on selectin binding inhibitos : Synthesis of sialyl-LeX and sialyl-LeA epitope analogs containing 2-acetamido deriv." J. Carbohydr. Chem.15 (1). 1-14 (1996)

M. Kiso：“选择素结合抑制剂的研究：含有 2-乙酰氨基衍生物的 sialyl-LeX 和 sialyl-LeA 表位类似物的合成。”

L.J.-S.Yang: "Gangliosides are neuronal ligands for myelin-associated glycoprotein" Proc.Natl.Acad.Sci.USA. 93. 814-818 (1996)

L.J.-S.Yang：“神经节苷脂是髓磷脂相关糖蛋白的神经元配体”Proc.Natl.Acad.Sci.USA。

G.Xu: "Sialidase of swine influenza A viruses: variation of the recognition specificities for sialyl linkages and for the molecular" Glycoconjugate J.12. 156-161 (1995)

G.Xu：“猪甲型流感病毒的唾液酸酶：唾液酸键和分子的识别特异性的变化”糖缀合物 J.12。