Chemical modification of oligosaccharide chains of N-aspargine-type glycoproteins

N-天冬酰胺型糖蛋白寡糖链的化学修饰

• 批准号: 06453142
• 负责人: OGAWA Seiichiro
• 金额: $ 3.58万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06453142/
• 关键词: Carbohydrate mimics; Carba-sugars; Pseudo-sugars; Cyclitols; Glycosidase inhibitors; Glycosyltransferases; Carbaoligosaccharides; カルバ糖(擬似糖); カルバ糖(擬似糖質)

In recent years, oligosaccharide-chains involved in complex glycoconjugates existing on a cell surface have attracted much attention of many researchers in various fields of biochemistry and organic chemistry. Therefore, in order to elucidate roles of oligosaccharide-chains, extensive studies have so far been carried out, and biologically very interesting results have been accumulated.In the present study, carbohydrate-mimicking pseudo-oligosaccharides were designed and synthesized in order to provide chemical tools which may be useful to study roles of glycosidases and glycosyltransferases involved in biosynthesis of such complex oligosaccharide-chanins fo cell-surface glycanes. Several carba-disaccharides and trisaccharides containing carba-sugar residues bonded by way of imino-, ether and sulfide linkages have been newly synthesized and subjected to biological assay. In general, imino-linked carba-oligosaccharides were shown to possess inhibitory action against glycosidases, whereas the carba-oligosaccahrides linked by ether or sulfide-bridge were found to act rather as substrate analogs toward glycosyltransferases. The present results have opened up new opportunity for the design and synthesis of inhibitors for enzymes. Since carba-sugars are chemically very stable cyclitol derivstives but have close similarlity toward three-dimensional structures of true sugars, different kind of chemical modification may be possibly designed for carba-sugar residues.The present studies have been collaborated with biochemistry professors, Drs.Hindsgaul and Palcic (University of Alberta, Canada), and our synthesized carbohydrate mimics of biological interests seem to assist and contribute to their extensive studies on sugar hydrolases and transferases for important oligosaccharide-chains in future.

近年来，生物化学和有机化学领域中涉及细胞表面复杂糖偶联物的寡糖链引起了众多研究人员的关注。因此，为了阐明寡糖链的作用，到目前为止，人们已经进行了广泛的研究，并积累了非常有趣的生物学结果。在本研究中，我们设计并合成了模拟碳水化合物的拟低聚糖，以期为研究糖苷酶和糖基转移酶在细胞表面甘蔗低聚糖-查宁生物合成中的作用提供化学工具。新合成了几种以亚氨基、乙醚和硫键为键的碳二糖和三糖，并进行了生物测定。一般来说，亚氨基连接的碳寡糖对糖苷酶有抑制作用，而乙醚或硫桥连接的碳寡糖则对糖基转移酶起底物类似物的作用。本研究结果为酶抑制剂的设计和合成提供了新的机遇。由于碳水化合物是化学上非常稳定的环状醇衍生物，但与真糖的三维结构非常相似，因此可能会针对碳水化合物残留物设计不同的化学修饰。目前的研究已与生物化学教授Hindsgaul博士和Palcic博士(加拿大阿尔伯塔大学)合作，我们合成的具有生物学意义的碳水化合物仿制品似乎有助于他们未来对糖水解酶和重要寡糖链转移酶的广泛研究。

项目成果

S.Ogawa, K.Hirai, T.Yamazaki, A.Nakajima, N.Matsunaga: "Synthesis of methyl 5a'-carba-beta-lactosides" Carbohydrate Letters. 183-188 (1996)

S.Okawa、K.Hirai、T.Yamazaki、A.Nakajima、N.Matsunaga：“甲基 5a-carba-β-乳糖苷的合成”碳水化合物快报。

S. Ogawa, T. Furuya, H. Tsunoda: "Synthesis of β-D-GlcpNAc- (1→2) 5a-carba-α-D-Manp- (1→6) -β-D-Glcp-O(CH_2) CH_3: A Reactive Acceptor Analog for GlcNAcT-V" Carbohydrate Research. 271. 197-205 (1995)

S. Okawa、T. Furuya、H. Tsunoda：“β-D-GlcpNAc- (1→2) 5a-carba-α-D-Manp- (1→6) -β-D-Glcp-O( 的合成CH_2) CH_3：用于 GlcNAcT-V" 碳水化合物研究的反应性受体类似物。271. 197-205 (1995)

S.Ogawa,T.Furuya,H.Tsunoda: "Synthesis of β-D-GlopNAc-(1→2)-5a-carba-α-D-Manp-(1→6)-β-D-Glcp-O(CH_2)_7CH_3" Carbohydrate Research. 271. 197-205 (1995)

S. Okawa、T. Furuya、H. Tsunoda：“β-D-GlopNAc-(1→2)-5a-carba-α-D-Manp-(1→6)-β-D-Glcp-O 的合成(CH_2)_7CH_3”碳水化合物研究。271. 197-205 (1995)

H.Tsunoda,S.Sasaki,T.Furuya,S.Ogawa: "Synthesis of Methyl 5a′-Carbamaltoses Linked by Imino,Ether and Sulfide Bridges and Unsaturated Derivatives Thereof" Liebigs Annalen der Chemie. 159-165 (1996)

H. Tsunoda、S. Sasaki、T. Furuya、S. Okawa：“通过亚氨基、醚和硫桥连接的甲基 5a-氨基麦芽糖及其不饱和衍生物的合成”Liebigs Annalen der Chemie 159-165 (1996)。

S.Ogawa,K.Hirai,T.Yamazaki,A.Nakajima,N.Matsunaga: "Synthesis of Methyl 5a′-Carba-β-lactosides" Carbohydrate Letters. 2. 183-188 (1996)

S. Okawa、K. Hirai、T. Yamazaki、A. Nakajima、N. Matsunaga：“甲基 5a′-Carba-β-乳糖苷的合成”碳水化合物快报。2. 183-188 (1996)