Basic Research on Discovery and Functions of Novel Physiologically Active Complex Carbohydrates

新型生理活性复合碳水化合物的发现及功能基础研究

基本信息

批准号：
12306007
负责人：
KISO Makoto
金额：
$ 22.08万
依托单位：
Gifu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12306007/
关键词：
selectin ganglioside sialic acid sialyl Lewis X sialyl Lewis A siglec CD38 glycolipids シアロ糖鎖シアリルルイスメ O-グリコシド型糖鎖フコシルトランスフェラーゼ α-シリーズガングリオシド

项目摘要

[1]Systematic synthesis of newly discovered sulfated sialyl Lewis X variants and elucidation of a novel immunity regulation system : It has been demonstrated at the molecular level, for the first time, that the de-N-acetylation of sialic acid (activation) and lactamization (inactivation) are the key reactions in the L-selectin ligand processing by the systematic precise synthesis (Carbohydr.Res.,338,2793-2812,2003). Thus, the highly efficient total synthesis of sialyl 6-O-sulfo Lewis X hexasaccharide gangliosides and sialyl 6-O-sulfo paraglobosides containing the de-N-acetylated and lactamized sialic acids have successfully carried out. By using the ~ synthesized ganglioside probes, the lactamized-sialyl 6-O-sulfo Lewis X was identified to be a major determinant recognized by G159 monoclonal antibody.[2]A novel sulfated ganglioside GSC-338 designed from α-series hybrid-type ganglioside has been found to be a super-high affinity ligand of myelin-associated glycoprotein (MAG), a neural siglec 4a (Carbohydr.Res.,338,1621-1639,2003). It has also been found that GSC-338 is a potent inhibitor of CD38 NADase expressed on leukocytes (Bioorg.Med.Chem.Lett.,13,3441-3445,2003).[3]The first total synthesis of α-(2-3)/α(2-6)-disialyl lactotetraosyl ceramide and disialyl Lewis X ganglioside as cancer-associated carbohydrate antigents has been carried out (Carbohydr. Res.,338,503-514,2003). The biosynthetic route and the expected functions were elucidated at the molecular level (J.Biol.Chem.,278,22787-22794,2003)

[1] Systematic synthesis of newly discovered sulfated sialyl Lewis X variants and elucidation of a novel immunity regulation system: It has been demonstrated at the molecular level, for the first time, that the de-N-acetylation of sialic acid (activation) and lactamiization (inactivation) are the key reactions in the L-selectin ligand processing by the systematic precision synthesis （碳水化合物，338,2793-2812,2003）。这是，高效的6-O-Sulfo Lewis X HexasAcachlide Gangliosides和含有含有De-N-乙酰化和乳乳化唾液酸的硫糖6- O-硫酸副糖苷的高效总合成已成功地进行了。 By using the ~ synthesized gangliosides, the lactmized-sialyl 6-O-sulfo Lewis X was identified to be a major determined recognized by G159 monoclonal antibody.[2]A novel sulfated ganglioside GSC-338 designed from α-series hybrid-type ganglioside has been found to be a super-high affinity ligand of myelin-associated糖蛋白（MAG），神经Siglec 4a（碳水化合物，338,1621-1639,2003）。还发现GSC-338是在白细胞上表达的CD38 NADase的潜在抑制剂（Bioorg.Med.Chem.Lelett。，13,3441-3445,2003）。已经进行了神经节苷脂作为癌症相关的碳水化合物抗体（Carbohydr。s。，338,503-514,2003）。在分子水平上阐明了生物合成途径和预期功能（J.Biol.Chem。，278,22787-22794,2003）