Technological development of oligosaccharide units as biomaterials of life science

低聚糖单元作为生命科学生物材料的技术进展

• 批准号: 09556021
• 负责人: USUI Taichi
• 金额: $ 7.3万
• 依托单位: Shizuoka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09556021/
• 关键词: Glycotechnology; Biomaterial; Glycoconjugate; Oligosacchride unit; Enzymatic synthesis; Glycopolymer; Molecular recognition; Molecular design; Oligosaccharide unit; Glycopolymor; Oligosaccharide library; Oligosaccharide Unit; Enzymatic Synthes

Our purpose is to prepare oligosaccharide units library folowing practical synthesis of biologically important oligosaccharides essentially for developing glycobology and glycottechnolog. The synthesis of possible array of linkages of (1-3), (1-4) and (1-6) of β-D-Gal-D-GlcNAc and β-D-Gal-D-GalNAc was done by using some readily available β-D-galactosidases. The preparation of the galactosyl-disaccharide units library led to the enzymatic synthesis of trisaccharides containing GlcNAc; β-D-GlcNAc-(1-3)-β-D-Gal-(1-4)-GlcNAc as a common unit of polylacto- saminoglycan and β-D-Gal-(1-3)-[β-D-GlcNAc-(1-6)]-α-D-GalNAc-OCィイD26ィエD2HィイD24ィエD2NOィイD22ィエD2-p as a carbohydrate unit of mucin type 2 core. Transglycosylation of L-Fuc to LacNAc and lactose utilizing α-L-fucosidases also produced α-L-fucosyl-N-acetyllactosamine and 3'-O-α-L-fucosyllactose. Furthermore, as a synthetic strategy of human milk oligosaccharide, lacto-N-tetraose (β-D-Gal-(1-3)-β-D-GlcNAc-(1-3)-β-D-Gal-(1-4)-D-Glc)and lacto-N-neotetraose(β-D-Gal-(1-4)-β-D-GlcNAc-(1-3)-β-D-Gal-(1-4)-D-Glc) were practically synthesized by a combination of glycosyltransferase catalyzed reaction and glycosidase-catalyzed transglycosylation from lactose as an initial substance.Such synthetic oligosaccharides available in large amounts were used to synthesize glycopolymer. chemo-enzymatic synthesis of glycopeptides carrying LacNAc unit as a model of asialoglycoprotein, and β-D-Gal-(1-3)-α-D-GalNAc and α-NeuAc-(1-3)-β-D-Gal-(1-3)-α-D-GalNAc units as models of mucin-type glycoproteins was carried out by introducing these oigosaccharides as side chain into polyglutamic acid as main chain. The artgificial glycopolypeptides were shown to be useful as probes of carbohydrate recognition and modeling in the analysis of glycoprotein-lectin interactions.

我们的目的是在实际合成具有重要生物学意义的低聚糖后，制备低聚糖单元库，主要用于糖学和糖技术的发展。利用一些现成的β- d -半乳糖苷酶合成了β-D-Gal-D-GlcNAc和β-D-Gal-D-GalNAc的（1-3）、（1-4）和（1-6）可能的键阵。半乳糖-二糖单元库的制备导致了含GlcNAc的三糖的酶促合成；β-D-GlcNAc-(1-3)-β-D-Gal-(1-4)- glcnac是聚乳酸-氨基聚糖的共同单位，β-D-Gal-(1-3)-[β-D-GlcNAc-(1-6)]-α- d - galnac - oc是粘蛋白2型核的碳水化合物单位。利用α-L- focusidase将L-Fuc转糖基化为LacNAc和乳糖也产生α-L- focusyl- n -乙酰乳胺和3'- o -α-L- focusyllactose。此外，作为人乳低聚糖的合成策略，以乳糖为起始物质，通过糖基转移酶催化反应和糖苷酶催化转糖基化反应，实际合成了乳酸-n -四糖(β-D-Gal-(1-3)-β- d - glcnac -(1-3)-β-D-Gal-(1-4)- (1-4)- d - glc)和乳酸-n -新四糖(β-D-Gal-(1-4)- β-D-Gal-(1-3)- β-D-Gal-(1-4)- d - glc)。这种合成的低聚糖大量可用来合成糖共聚物。将低聚糖作为侧链引入聚谷氨酸作为主链，以LacNAc单元为asialalprotein模型，以β-D-Gal-(1-3)-α- d - galnac和α-NeuAc-(1-3)-β-D-Gal-(1-3)-α- d - galnac单元为黏液型糖蛋白模型的糖肽进行化学酶合成。人工糖共肽在糖蛋白-凝集素相互作用分析中被证明是有用的碳水化合物识别和建模探针。

项目成果

T.Murata, T.Usui et al: "Facile enzymatc conversion of lactose into lacto-N-tetraose and lacto-N-tetraose"Glycoconjugate Journal. 16. 189-195 (1999)

T.Murata、T.Usui 等人：“将乳糖轻松酶促转化为乳糖-N-四糖和乳糖-N-四糖”糖复合物杂志。

Murata,T.,Shimada M.,Watanabe N.,Sakata K.,and Usui T.: "Practical enzymatic synthesis of primeverose annd its glycoside"J.Appl.Glycosci.. 46. 431-437 (1999)

Murata,T.,Shimada M.,Watanabe N.,Sakata K.,and Usui T.:“春花及其糖苷的实用酶促合成”J.Appl.Glycosci.. 46. 431-437 (1999)

T. Murata, T. Inukai, T. Suzuki, S. M. Yamagishi and T. Usui: "Facile enzymatc conversion of lactose into lacto-N-tetraose and lacto-N-tetraose"Glycoconjugate J.. 16. 189-195 (1999)

T. Murata、T. Inukai、T. Suzuki、S. M. Yamagishi 和 T. Usui：“将乳糖轻松酶促转化为乳糖-N-四糖和乳糖-N-四糖”Glycoconjugate J.. 16. 189-195 (1999)

T. Murata, T. Itoh and T. Usui: "Enzymatic synthesis of β-D-Gal-(1-3)-[β-D-GlcNAc-(1-6)]-α-D-GalNAc-OCィイD26ィエD2HィイD24ィエD2NOィイD22ィエD2-pas a carbohydrate unit of mucin-type 2 core"Glycoconjugate J.. 15. 575-582 (1998)

T. Murata、T. Itoh 和 T. Usui：“β-D-Gal-(1-3)-[β-D-GlcNAc-(1-6)]-α-D-GalNAc-OC 的酶促合成” D26 D2H D24 D2NO D22 D2-pas 粘蛋白型 2 核心的碳水化合物单元”Glycoconjugate J.. 15. 575-582 (1998)

T. Usui: ""Synthesis of glycan chain using enzyme" (in Japanese)""Research of biological active glycan" ed by Gakaishuppan center.

T. Usui：“利用酶合成聚糖链”（日语）“生物活性聚糖的研究”，Gakaishuppan 中心编辑。