Multivalent Presentation of Mannose on Hyperbranched Polyglycerol and their Interaction with Concanavalin A Lectin
Multivalent Presentation of Mannose on Hyperbranched Polyglycerol and their Interaction with Concanavalin A Lectin
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DOI：
10.1002/cbic.201000718
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发表时间：
2011-05-02
期刊：
影响因子：
3.2
通讯作者：
Haag, Rainer
中科院分区：
文献类型：
--
作者：
Papp, Ilona;Dernedde, Jens;Haag, Rainer
我们描述了使用超支化聚甘油（hPG）作为具有不同接头结构的支架来合成多价甘露糖衍生物。受保护的甘露糖 (Man) 单元的接枝是通过使用 Cu-1 催化的 Huisgen 点击化学与异头叠氮化物或炔丙醚到互补功能化的炔或叠氮聚合物表面来实现的。 NMR 光谱、动态光散射 (DLS)、红外光谱、尺寸排阻色谱 (SEC) 和元素分析已用于表征 hPG-Man 化合物。通过使用基于竞争性表面等离振子共振 (SPR) 的结合测定，通过糖聚合物与刀豆球蛋白 A (Con A)（一种结合含甘露糖分子的凝集素）的相互作用来评估 Man 修饰聚合物的表面可用性和生物活性。结果表明，这项工作中提出的新型糖结构是Con A-甘露糖识别的有效抑制剂，抑制剂浓度（平均IC50）从微摩尔到纳摩尔范围，而相应的单价甘露糖苷（甲基-Man）需要毫摩尔浓度。结果为生物相容性聚甘油支架上存在的糖部分的连接不同的材料库提供了有趣的结构-活性关系。
We describe the synthesis of multivalent mannose derivatives by using hyperbranched polyglycerols (hPG) as a scaffold with different linker structures. Grafting of protected mannose (Man) units is achieved by using Cu-1-catalyzed Huisgen click chemistry with either an anomeric azide or propargyl ether onto complementarily functionalized alkyne or azido polymer surfaces. NMR spectroscopy, dynamic light scattering (DLS), IR spectroscopy, size-exclusion chromatography (SEC), and elemental analysis have been used to characterize the hPG-Man compounds. The surface availability and bioactivity of Man-modified polymers were evaluated by using a competitive surface plasmon resonance (SPR)-based binding assay by interactions of the glycopolymers with concanavalin A (Con A), a lectin that binds mannose containing molecules. The results indicated that the novel glycoarchitectures presented in this work are efficient inhibitors of Con A-mannose recognition and resulted in inhibitor concentrations (mean IC50) from the micro-to the nanomolar range, whereas the corresponding monovalent mannoside (methyl-Man) requires millimolar concentrations. The results provide an interesting structure-activity relationship for libraries of materials that differ in the linkage of the sugar moiety presented on a biocompatible polyglycerol scaffold.