苝-环糊精-糖类超分子多效价糖基组装体的构筑、识别和靶向给药研究

The development of novel functional supramolecular assemblies based on bioactive building blocks has become one of the fastest growing fields of chemistry, materils, biologicy and medicine. Based on the biological actives of multivalent glycoclusters, the selective and specific binding interactions of carbohydrate-protein, the strong aggregated ability and the characteristic of the regulation of the aggregation behaviors and fluorescence properties of perylene bisimides, combined with the complexation interactions of cyclodextrins with guests, a series of mantose and lactose modified perylene bisimide-cyclodextrin-carbohydrate derivatives will be designed and synthesized. Furthermore, novel multivalent glycoclusters and hetero-glycoclusters were fabricated through supramolecular methods (includeing molecular self-assembly and complexation interactions of host-guest), and their binding interactions with lectins, E. coli strains and tumor cells, and their potential application in the field of targeted drug delivery system were investigated. Through the above research, novel biocompatible recognition and sesing systems, the relationships between the structures of the supramolecular multivalent glycoclusters and hetero-glycoclusters with the functions, and novel glycoproteins and glycolipids will be developed and found. Moreover,the multivalent glycoclusters and hetero-glycoclusters possess potential applications as anti-infective, anti-viral, anti-immune drugs, human vaccines and targeted drug delivery systems.

以生物学功能为导向的特殊功能超分子组装体的构筑和性质研究在化学、材料、生物和药物化学等领域具有重要应用。本课题基于多效价糖基配体广泛的生物活性、糖-蛋白高度专一的识别和粘附作用，苝酰亚胺类分子强的自组装能力、可调控的聚集行为和荧光性质，结合环糊精分子选择性识别客体分子的能力，设计合成新型水溶性苝酰亚胺-环糊精-糖类衍生物，通过将自组装、疏水作用和主客体分子络合作用等多种超分子方法相结合构筑超分子多效价糖基配体和杂糖配体组装体，研究其与凝集素、大肠杆菌和肿瘤细胞等的相互作用和生物活性，进而开展基于超分子多效价糖基配体组装体的靶向给药体系的应用研究。通过以上研究工作，开发生物相容的识别和传感体系，模拟生物组装体的功能，为新型超分子多效价糖基和杂糖基配体组装体的研究提供新的方法和途径，为新型抗感染、抗病毒、抗免疫药物和人体疫苗的研究，以及靶向给药研究提供理论基础和技术支持。

以生物学功能为导向的特殊功能超分子组装体构筑和性质研究在化学、材料、生物和药物化学领域具有重要应用。本课题基于多效价糖基配体广泛的生物活性、糖-蛋白高度专一的识别和粘附作用，苝酰亚胺类分子强的自组装能力和可调控的聚集行为和荧光性质，结合环糊精分子对客体分子选择性键合作用，合成了多个系列的水溶性苝酰亚胺-糖类化合物和苝酰亚胺-环糊精-糖类化合物。分别实现了对凝集素分子和巨噬细胞的专一性识别；经自组装构筑了手性超分子多效价糖基组装体，实现了可预测的超分子手性研究，即酰亚胺处为单糖时形成左手特征的超分子手性，为二糖时形成右手特征的超分子手性。另外，海湾处侧链链接方式也能调控超分子手性；经自组装构筑了具有excimer态的超分子组装体，实现了对人提取指纹的显色；由于环糊精分子的自包结作用，构筑了具有光动力学治疗体系，实现了对肿瘤细胞的成像和治疗；经主客体分子络合作用，实现了可调控的蛋白分子的捕获和释放。通过以上研究工作，为开发生物相容的识别和传感体系，为新型超分子多效价糖基组装体研究提供了新的方法和途径，为基于糖类分子的靶向给药研究提供理论基础和技术支持。