Synthesis and application of biologically-active multivalent-polymers

生物活性多价聚合物的合成及应用

• 批准号: 12558076
• 负责人: ARIMOTO Hirokazu
• 金额: $ 8.45万
• 依托单位: NAGOYA UNIVERSITY (2001-2002)Shizuoka University (2000)
• 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 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12558076/
• 关键词: biological activity; polymer; バンコマイシン; 集積化; 医薬品; 耐性菌

Synthesis of multi-valent polymer of glycopeptide antibiotics, vancomycin was investigated. The polymers exhibited enhanced antibacterial activity against vancomycin-resistant enterococci (VRE). The reaction conditions were optimized first, so that the polymers with different degree of polymerization could be obtained. Surface plasmon resonance study proved that the affinity between vancomycin polymers and bacterial cell wall precursors was greatly enhanced. The increased affinity would be important in antibacterial activity toward resistant bacteria. We synthesized block-copolymers of vancomycin and series of hydrophilic compounds.Analytical method for these polymers was also investigated. Dynamic light scattering was found to be suitable for rapid and quantitative determinations of the degree of polymerizations.Design and synthesis of oligomeric compounds anti-prion disease or anti-cancer were also done. These samples are under evaluations.

研究了糖肽抗生素万古霉素多价聚合物的合成。该聚合物对耐万古霉素肠球菌（VRE）表现出增强的抗菌活性。首先优化反应条件，得到不同聚合度的聚合物。表面等离子体共振研究证明万古霉素聚合物与细菌细胞壁前体之间的亲和力大大增强。增加的亲和力对于抵抗细菌的抗菌活性非常重要。我们合成了万古霉素和一系列亲水性化合物的嵌段共聚物，并对这些聚合物的分析方法进行了研究。发现动态光散射适合于聚合度的快速定量测定。还进行了抗朊病毒病或抗癌寡聚化合物的设计和合成。这些样品正在评估中。

项目成果

A.B.Smith, III et al.: "Evolution of a gram-scale synthesis of (+)-discodermolide"J.Am.Chem.Soc.. 122. 8654-8664 (2000)

A.B.Smith, III 等人：“( )-discodermolide 的克级合成的演化”J.Am.Chem.Soc.. 122. 8654-8664 (2000)

H.Arimoto: "Multi-valent polymer of vancomycin with enhanced antibacterial activity against VRE"Pharmacia. 479-483 (2000)

H.Arimoto：“万古霉素多价聚合物，对 VRE 具有增强的抗菌活性”Pharmacia。

Hirokazu Arimoto et al.: "Affinity of a vancomycin-polymer with Bacterial Surface Models"Tetrahedron Letters. (印刷中). (2001)

Hirokazu Arimoto 等人：“万古霉素聚合物与细菌表面模型的亲和力”四面体快报（印刷中）。

I.Hayakawa, H.Arimoto, D.Uemura: "SYNTHESIS OF (±) -PINNAIC ACID"Heterocycles. 59(印刷中). (2003)

I.Hayakawa、H.Arimoto、D.Uemura：“(±)-蒎酸的合成”59（印刷中）。

H.Kawagishi et al.: "Liver Injury Suppressing Compounds from Avocado"J.Agric. Food Chem.. 49. 2215-2221 (2001)

H.Kawagishi 等人：“鳄梨中的肝损伤抑制化合物”J.Agric。