Development of glyco-cluster materials systems to detect and neutralize pathogenic microorganisms

开发检测和中和病原微生物的糖簇材料系统

• 批准号: 13558108
• 负责人: KOBAYASHI Kazukiyo
• 金额: $ 8.19万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13558108/
• 关键词: carbohydrates; biomaterials; polymers; molecular recognition; influenza virus; vero toxins; ruthenium complexes; インフルエンザウィルス

Influenza viruses and pathogenic E.coli species are epidemic and sometimes critical for infants and aged patients. These pathogens invade our bodies through cell surface oligosaccharides. Sialo oligoaccharides and α(l-4)-galactobiosyl oligosaccharides on cell surfaces are the recovnition signals respectively for influenza viruses and E.coli Shiga toxins (Stx-I and Stx-II). The present research is aimed at developing polymer-based biomaterials having multivalent sialo and α(l-4)-Gal arrays to detect, capture, and neutralize influenza-viruses and vero toxins.We have succeeded in one-pot transglycosylation of disialo complex-type oligosaccharides onto an α-glucose-functionalized tris-bipyridine ruthenium complex. The resulting glycoconjugates exhibited excellent lectin-affinities comparable to that of polymers presenting multiple sialoside arrays. Also, they have strong luminescence that is markedly depressed by addition of virus, probably due to disruption of their saccharide-shell structures.We have found the potential utility of the galacto-trehalose α(l-l)-linkage as a promising substitute for the globosyl α(l-4)-linkage. Though the binding of the galacto-trehalose to Stx-I and Stx-II, particularly to the latter, is still weaker than that of the natural Gb_2 and Gb_3 globosides, galacto-trehalose may integrate the binding affinity significantly by additionally introducing β-glucoside moiety or related other units.

流感病毒和致病性大肠杆菌是流行病，有时对婴儿和老年患者至关重要，这些病原体通过细胞表面寡糖和 α(1-4)-半乳二糖基寡糖分别作为识别信号侵入我们的身体。流感病毒和大肠杆菌志贺毒素（Stx-I 和 Stx-II）目前的研究旨在开发具有聚合物基的生物材料。多价唾液酸和 α(l-4)-Gal 阵列用于检测、捕获和中和流感病毒和维罗毒素。我们已成功将二唾液酸复合型寡糖一锅转糖基到 α-葡萄糖功能化的三联吡啶上所得的糖复合物表现出与呈现多个唾液酸苷阵列的聚合物相当的优异的凝集素亲和力。添加病毒后发光明显减弱，可能是由于其糖壳结构的破坏。我们发现半乳糖-海藻糖 α(l-l)-连接作为球糖基 α(l-4) 有前景的替代品的潜在用途尽管半乳海藻糖与 Stx-I 和 Stx-II（尤其是后者）的结合仍然弱于天然 Gb_2 和 Stx-II 的结合。 Gb_3球苷、半乳海藻糖可以通过额外引入β-葡萄糖苷部分或相关其他单元来显着整合结合亲和力。

项目成果

T.Hasegawa, T.Yonemura, K.Kobayashi: "Tris-bipyridine ruthernium complex-based glyco clusters"Tetrahedron Lett.. 42. 3989-3992 (2001)

T.Hasekawa、T.Yonemura、K.Kobayashi：“基于三联吡啶钌复合物的糖簇”Tetrahedron Lett.. 42. 3989-3992 (2001)

H.Tanaka, Y.Nishida, K.Kobayashi: "A Convenient Synthetic Pathway for Multivalent Assembly of Aminoglycoside Antibiotics Starting from Amikacin"Medicinal Chem.Lett.. 310. 27-35 (2002)

H.Tanaka、Y.Nishida、K.Kobayashi：“从阿米卡星开始的氨基糖苷类抗生素多价组装的便捷合成途径”Medicinal Chem.Lett.. 310. 27-35 (2002)

Y.Shingu, Y.Nishida, H.Dohi, K.Matsuda, K.Kobayashi: "Convenient access to halide ion-catalysed alpha-glycosylation free from noxious fumes at the donor synthesis"J.Carbohydr.Chem.. 21. 605-611 (2002)

Y.Shingu、Y.Nishida、H.Dohi、K.Matsuda、K.Kobayashi：“在供体合成中方便地进行卤离子催化的 α-糖基化，且无有毒烟雾”J.CarboHydr.Chem.. 21. 605

H.Kato, A.Yashiro, K.Kobayashi: "Synthesis and Biological Evaluations of α-D-Mannosyl[60]Fullerenols"Bioorg.Medicinal Chem.Lett.,. 11. 2935-2939 (2001)

H.Kato、A.Yashiro、K.Kobayashi：“α-D-甘露糖基[60]富勒烯醇的合成和生物学评价”Bioorg.Medicinal Chem.Lett.，11. 2935-2939 (2001)

H.Dohi, Y.Nishida, K.Kobayashi: "Biological potential of galacto-type trehalose"Org.Lett.. 4. 355-357 (2002)

H.Dohi、Y.Nishida、K.Kobayashi：“半乳糖型海藻糖的生物潜力”Org.Lett.. 4. 355-357 (2002)