多级可控组装模拟生物体系的功能

项目名称： 多级可控组装模拟生物体系的功能

项目编号： No.91527306

项目类型： 重大研究计划

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 史林启

作者单位： 南开大学

项目金额： 320万元

中文摘要： 通过化学多级组装模拟生物体系的结构和功能，获得具有生物活性功能的组装材料，揭示化学组装结构与生物功能之间的关系，探索重大疾病的精准诊断与高效治疗新模式。包括可控复合组装模拟分子伴侣的结构与功能制备多功能协同的人工分子伴侣，用于调控蛋白质折叠，重点探索其体内高效识别及选择性结合Aβ蛋白的功能，通过抑制Aβ蛋白的聚集、降低其神经细胞毒性、促进Aβ蛋白降解以及纤维化Aβ蛋白的解离，探索治疗阿尔茨海默症的新方法。模拟生物体系的自适应功能，通过组装与解组装的过程适应不同生理过程的要求，利用需要时触发生物组装体发挥其特定功能作用的策略，为疾病精准治疗提供了新方法与新模式，解决癌症化疗和细菌的抗药性问题。将人工分子伴侣与生物标记技术相结合，通过人工分子伴侣选择性结合Aβ蛋白后，激发超分子光敏剂发出特定的荧光，实现高灵敏度检测Aβ蛋白，结合动物试验的结果发展退行性神经疾

中文关键词： 仿生自组装；人工分子伴侣；阿兹海默症；自适应；抗药性

英文摘要： Simulating the structure and function of biosystems through chemically hierarchical assembly can contribute to obtaining assembled materials with bioactive functions, revealing the relationship between chemically assembled structures and biological functions, and ultimately, exploring new modes for accurate diagnosis and effective treatment of major diseases. Among them, mimicking the structure and function of molecular chaperone via the controllable composited assembly can guide us to prepare multi-functionally synergistic artificial molecular chaperone. It will be applied to regulate the protein folding, explore its effective recognition and selective binding to Aβ protein in vivo. Furthermore, new methods for the treatment of Alzheimer's disease can be developed by means of suppressing Aβ protein aggregation, reducing the neurotoxicity of Aβ protein, as well as promoting the degradation of Aβ protein and dissociation of fibrotic Aβ protein. Moreover, in order to simulate the adaptive function of biosystem and meet the requirements of different physiological processes, we utilized the assembly-disassembly process and adopted the strategy that the specific functions of biological assemblies can be triggered only when required. Sequentially, new methods and patterns for precise disease treatments can be constructed, such as cancer chemotherapy and drug resistance issue of anti-microbial. Combining the technique of artificial molecular chaperone and biomarkers, when artificial molecular chaperone selectively binds to Aβ protein, specific fluorescence can be achieved by exciting supramolecular photosensitizer, therefore, high sensitive detection of Aβ protein can be realized. Significantly, combined with the result of animal test, new techniques of early accurate diagnosis of neurodegenerative diseases can be greatly developed.

英文关键词： Biomimetic self-assembly;Artificial chaperone;Alzheimer's disease;Self-adaption;Drug resistance