Development of Scientific Basics of New Polymer-Drugs Based on Sugar Balls

基于糖球的新型高分子药物的科学基础开发

• 批准号: 12555259
• 负责人: AOI Keigo
• 金额: $ 3.97万
• 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: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12555259/
• 关键词: dendrimer; sugar ball; polypeptide; molecular recognitions; molecular capsule; carbohydrate polymer; biomedical materials; DNA

The present study is concerned with synthesis of sugar/lipid-hybrid sugar balls and reading of a guest molecule into the host molecule. Galactose-bearing glycopeptide-type sugar ball capsule was designed, which was expected to interact with liver cell specifically. Polymer reaction of poly(amido amine) dendrimer with peracetylated sugar-substituted serine N carboxyanhydride (NCA) was carried out in the presence of 8-anilino-l-naphthalenesulfonate (ANS) in chloroform at -30 ゜C for 15 min. Acyl groups were introduced to the terminal amino groups to form a hydrophobic layer.Then, the product was deacetylated with hydrazine monohydrate in methanol. UV and fluorescence measurements indicated that the existence of ANS inside the sugar ball capsule.Synthesis of "sugar cylinders", novel graft copolymers [poly(L-lysine)-graft glycopeptide-persubstituted poly(amido amine) dendrimer] was also carried out by the polymer reaction of poly(L-lysine)-graft-poly(amido amine) dendrimer with peracetylated N-acetyl-D glucosamine-substituted L-serine N-carboxyanhydride in chloroform at -30 ゜C, Functionality of the terminal amino groups in the polymer reaction was 1.0, which was determined by NMR spectro scopy.Cell recognition ability of the sugar ball/plasmid DNA complexes was examined by erythrocyte agglutination inhibition assays using wheat germ agglutinin (WGA). The minimum inhibitory concentrations of the sugar ball/DNA complexes were well fitted with those of corresponding sugar balls. The nuclease digestion of the complex by restriction endonucleases was investigated at 37 ゜C. DNA dissociated by poly(aspartic acid) appeared resistant to the nucleases.

本研究涉及糖/脂杂化糖球的合成和客体分子到主体分子中的阅读。设计了一种含半乳糖的糖肽型糖球胶囊，以期与肝细胞特异性结合。在8-苯胺基-1-萘磺酸盐（ANS）存在下，在氯仿中于-30 ℃下，聚酰胺-胺树状大分子与全乙酰化糖取代丝氨酸-N羧酸酐（NCA）反应15 min，在末端氨基上引入酰基形成疏水层，然后在甲醇中用一水合肼脱乙酰化。紫外光谱和荧光光谱分析表明，糖球囊内存在ANS。“糖柱”的合成，新型接枝共聚物[聚（L-赖氨酸）-接枝糖肽-全取代聚（酰胺胺）树枝状大分子]也进行了聚合反应的聚（L-赖氨酸）-接枝-聚（酰胺基胺）树状聚合物与全乙酰化的N-乙酰基-D葡糖胺-取代的L-丝氨酸N-羧酸酐在氯仿中在-30 ℃，用核磁共振（NMR）法测定了糖球/质粒DNA复合物的末端氨基官能度为1.0，用麦胚凝集素（WGA）法测定了糖球/质粒DNA复合物的红细胞凝集抑制能力。糖球/DNA复合物的最低抑菌浓度与相应糖球的最低抑菌浓度吻合良好。在37 ℃下研究了限制性内切酶对复合物的核酸酶切。用聚天冬氨酸解离的DNA对核酸酶有抗性。

项目成果

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K.Aoi: "Nano-scale molecular shapes of water-soluble chitin derivatives having monodisperse poly(2-alkyl-2-oxazoline) side chains"Macromolecular Chemistry and Physics. (印刷中).

K.Aoi：“具有单分散聚（2-烷基-2-恶唑啉）侧链的水溶性甲壳素衍生物的纳米级分子形状”《高分子化学与物理》（出版中）。

H. Sato: "Determination of Degree of Substitution of N-Carboxyethylated Chitin Derivatives by Pyrolysis-Gas Chromatography in the Presence of Oxalic Acid"Journal of Analytical and Applied Pyrolysis. (印刷中).

H. Sato：“在草酸存在下通过热解-气相色谱法测定 N-羧乙基化甲壳素衍生物的取代度”分析与应用热解杂志（正在出版）。

青井啓悟: "シュガーボール:生化学・生医学への応用に向けて"化学と生物. 48・11. 751-754 (2000)

葵吾：“糖球：走向生物化学和生物医学”化学和生物学48・11（2000）。

K. Aoi, A. Takasu, M. Okada, T. Imae: "Nano-scale Molecular Shapes of Water-Soluble Chitin Derivatives Having Monodisperse Poly(2-alkyl-2-oxazoline) Side Chains"Macromolecular Chemistry and Physics. in press.

K. Aoi、A. Takasu、M. Okada、T. Imae：“具有单分散聚（2-烷基-2-恶唑啉）侧链的水溶性甲壳素衍生物的纳米级分子形状”高分子化学和物理。