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

• 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

[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刘易斯X变体的系统合成和新免疫调节系统的阐明：已经首次在分子水平上证明唾液酸的去N-乙酰化（活化）和内酰胺化（失活）是通过系统精确合成的L-选择素配体加工中的关键反应（Carbohydr.Res.，338，2793 - 2812，2003）。因此，成功地进行了含有去N-乙酰化和内酰胺化唾液酸的唾液酸6-O-磺基刘易斯X六糖神经节苷脂和唾液酸6-O-磺基副神经节苷脂的高效全合成。利用合成的神经节苷脂探针，确定了6-O-磺基刘易斯X是G159单克隆抗体识别的主要决定簇。[2]A已经发现由α-系列混合型神经节苷脂设计的新的硫酸化神经节苷脂GSC-338是髓鞘相关糖蛋白（MAG），神经信号蛋白4a（Carbohydr.Res.，338，1621 - 1639，2003）。还发现GSC-338是白细胞上表达的CD 38 NAD酶的有效抑制剂（Bioorg.Med.Chem.Lett.，13，3441 - 3445，2003）。[3]已经进行了α-（2-3）/α（2-6）-二唾液酸乳糖四糖基神经酰胺和二唾液酸刘易斯X神经节苷脂作为癌症相关碳水化合物抗肿瘤剂的首次全合成（Carbohydr.结果：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）

项目成果

Mamelak, D.: "The aglycone of sulfogalactolipids can alter the sulfate ester substitution position required for hsc70 recognition."Carbohydr.Res.. 20. 91-100 (2001)

Mamelak, D.：“磺基半乳糖脂的糖苷配基可以改变 hsc70 识别所需的硫酸酯取代位置。”CarboHydr.Res.. 20. 91-100 (2001)

Otsubo, N.: "The first, efficient synthesis of novel sLe^x neoglycolipids containing N-deacetylated and lactamized sialic acid : key ligand structures for selectin binding"J.Carbohydr.Chem.. 20. 329-334 (2001)

Otsubo, N.：“首次有效合成含有 N-脱乙酰化和内酰胺化唾液酸的新型 sLe^x 新糖脂：选择素结合的关键配体结构”J.CarboHydr.Chem.. 20. 329-334 (2001)

Hubi, U.: "Studies on the specificity and sensitivity of the influeneza C virus binding assay for 9-O-acetylated sialic acids and its application to human melanomas."J.Biochem.. 127. 1021-1031 (2000)

Hubi, U.：“关于 9-O-乙酰化唾液酸的丙型流感病毒结合测定的特异性和敏感性及其在人类黑色素瘤中的应用的研究。”J.Biochem.. 127. 1021-1031 (2000)

Otsubo, N.: "The first, highly efficient synthesis of spacer-armed O-glycans on GlyCAM-1 and PSGL-1 : the counter-receptors for L- and P-selectin"Tetrahedron Lett.. 41. 3879-3882 (2000)

Otsubo, N.：“在 GlyCAM-1 和 PSGL-1 上首次高效合成间隔臂 O-聚糖：L-和 P-选择素的反受体”Tetrahedron Lett.. 41. 3879-3882 (

石田秀治: "糖鎖工学・設計酵素による糖鎖合成"農芸化学の事典""朝倉書店. 287-294 (2003)

Hideharu Ishida：“使用设计的酶进行糖工程/聚糖合成”农业化学百科全书”朝仓书店.287-294（2003）