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]新发现的硫酸化唾液酸Lewis X变体的系统合成和新型免疫调节系统的阐明：首次在分子水平上证明，唾液酸的脱N-乙酰化（激活）和内酰胺化（失活）是系统精确合成的 L-选择素配体加工中的关键反应(CarboHydr.Res.，338，2793-2812，2003)。因此，含有脱N-乙酰化和内酰胺化的唾液酸6-O-磺基Lewis X六糖神经节苷脂和唾液酸6-O-磺基副红细胞苷的高效全合成通过使用〜合成的神经节苷脂探针，成功地进行了唾液酸。内酰胺化唾液酸6-O-磺基Lewis X被鉴定为G159单克隆抗体识别的主要决定因素。[2]由α系列混合型神经节苷脂设计的新型硫酸化神经节苷脂GSC-338被发现具有超高的识别率。髓磷脂相关糖蛋白 (MAG) 的亲和配体，一种神经 siglec 4a (CarboHydr.Res.，338，1621-1639，2003)还发现GSC-338是白细胞上表达的CD38 NAD酶的有效抑制剂(Bioorg.Med.Chem.Lett.，13，3441-3445， 2003).[3]α-(2-3)/α(2-6)-二唾液酸的首次全合成乳四糖基神经酰胺和二唾液酰Lewis X神经节苷脂作为与癌症相关的碳水化合物抗原已经进行了研究(CarboHydr.Res.，338，503-514，2003，278，22787-22794，2003)。