Studies on glycan processing inhibitors

聚糖加工抑制剂的研究

• 批准号: 63560123
• 负责人: KISO Makoto
• 金额: $ 1.28万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-63560123/
• 关键词: N-acetylneuraminic acid; KDO; 1-deoxynojirimycin; complex carbohydrates; glycan processing; KDO誘導体

1. The 2-beta-SNa derivative of N-acetylneuraminic acid (Neu5Ac) was combined with cytidine, deoxycytidine and arabinosyl,cytosine, respectively, through the spacer-arms such as (a) -SCH_2O- and (b) -SCH_2CONH-, to give the corresponding CMP-Neu5Ac derivatives and analogs. These compounds showed the inhibition activity against Neu5Ac synthase and Neu5Ac transferase, and might be useful to analyze the biological functions of cell-surface sialo-glycoconjugates. The 2-beta-SNa derivative of 2-keto-3-deoxy-octonic acid (KDO) has, also been synthesized and combined with cytidine, deoxycytidine and arabinosyl cytosine, respectively, as described for Neu5Ac. The biological activities are now in investigation.2.1-Deoxynojirimycin (DNJ) was converted, via the epoxide intermediates, into a series of N-acetylhexosamine analogs, i. e., 2-acetamido-1,2,5-trideoxy-1,5-imino- D-glucitol (GlcNAcDNJ), -D-mannitol (ManNAcDNJ), -D-galactitol (GalNAcDNJ) and their isomers. The inhibition activity against the corresponding N-acetylhexosaminidase was examines. GlcNAcDNJ was further converted to the disaccharides related to lactose, lactosamine and chitobiose which are the prominent components of widespread glycoconjugates. More complex glycans containing DNJ as a reducing-end component will be designed.

1。分别通过诸如（（a）-sch_2o-和（b）-SCH_2Conh-- salibs serigs serigs and-nef-nef-nef-nef-nef-nef-nef-nef-nef-nef-nef-nef-nef-nef-nef-nef-nef-sch_2o-sch_2conh--，分别给出了n-乙酰神经酰胺酸（NEU5AC）的2-β-SNA衍生物（NEU5AC）分别与胞苷，二氧胞苷和阿拉伯糖苷相结合。这些化合物显示了对NEU5AC合酶和NEU5AC转移酶的抑制活性，并且可能有助于分析细胞表面sialo-糖缀合物的生物学功能。正如NEU5AC所述，分别合成了2-Keto-3-脱氧 - 辛酸（KDO）的2-SNNA衍生物，分别已合成并与胞苷，脱氧胞苷和阿拉伯糖基胞嘧啶合成。现在正在研究生物学活性。2.1-脱氧诺二霉素（DNJ）通过环氧中间体转化为一系列N-乙酰己糖胺类似物，i。 e。，2-乙酰胺-1,2,5-Trideoxy-1,5- imino-imino-d-d-葡萄醇（Glcnacdnj），-d-甘露醇（mannacdnj），-d- galactitol（galnacdnj）及其Isomers及其Isomers。研究了对相应的N-乙酰己糖胺酶的抑制活性。 Glcnacdnj进一步转化为与乳糖，乳糖胺和壳聚糖有关的二糖，这是广泛的糖缀合物的突出成分。将设计包含DNJ作为还原末端组件的更复杂的聚糖。

项目成果

Hasegawa,A.: "Synthetic studies on sialoglycoconjugates 4:synthesis of 5-acetamido-3,5-dideoxy-D-galacto-2-octulosonic acid derivatives and analogs." J.Carbohydr.Chem.8. 135-144 (1989)

Hasekawa,A.：“唾液酸糖缀合物 4 的合成研究：5-乙酰氨基-3,5-二脱氧-D-半乳糖-2-辛糖酸衍生物和类似物的合成。”

Kartha、K.P.R.: "Synthetic studies sialoglycoconjugates 9:an efficient method for the selective acetolysis of 2-(trimethylslyl)ethyl glycosides using ferric chloride in acetic anhydride." J.Carbohydr.Chem.8. 675-679 (1989)

Kartha, K.P.R.：“唾液酸糖缀合物 9 的合成研究：在乙酸酐中使用氯化铁选择性乙酰解 2-(三甲基甲硅烷基)乙基糖苷的有效方法。J.CarboHydr.Chem.8 (1989)。

Kiso,M.: "Studies on glycan processing inhibitors:synthesis of N-acetylhexosamine analogs of 1-deoxy-nojirimycin." J.Carbohydr.Chem.(1990)

Kiso,M.：“聚糖加工抑制剂的研究：1-脱氧野尻霉素的 N-乙酰己糖胺类似物的合成。”

Hasegawa, A., Ito, Y., Morita, M., Ishida, H. & Kiso, M.: "Synthetic studies on sialoglycoconjugates 4: synthesis of 5-acetamido-3,5-dideoxy-D-galacto-2-octulosonic acid derivatives and analogs." J. Carbohydr. Chem. 8: 135-144, 1989.

长谷川，A.，伊藤，Y.，森田，M.，石田，H.

Kartha、K.P.R.: "Synthetic studies toward gangliosides and their analogs;synthesis of appropriately protected core oligosaccharides ad construction blocks." J.Carbohydr.Chem.8. 145-158 (1989)

Kartha, K.P.R.：“神经节苷脂及其类似物的合成研究；适当保护的核心寡糖和结构单元的合成。J.CarboHydr.Chem.8 (1989)。”