藉配体识别决定区表面印迹构建人工受体选择性捕获鹅膏毒肽的研究

The selective recognition of bio-macromolecules has been a focus of scientific research in the field of separation and purification, drug delivery and medical diagnose. Mass accidents of mushroom poisoning occur often and couple with a high fatality rate, and amantins are the major toxins. The development of high affinity receptors for specific capturing amantins from the blood would be of great importance on patient treatment and rehabilitation. Among the various existing approaches to produces bio-mimetic systems for molecular recognition, molecular imprinting seems to be a promising way. However, the amantins is rather scarce and expensive，which hinder the preparation of artificial receptors through molecular imprinting technology. Inspired by the biological concept of ligands and receptor recognition, this project intends to carry out the following work: through refining the key recognition sites of amantins, we aims to design and synthesize a series of templates so that the novel surface imprinting biomimetic material could be constructed under optimal conditions. It is also crucial to explore the inner link that template structure, synthesis method and condition affect the composition, structure and function of the imprinting material. Furthermore, through exploring the recognition mechanism of the novel material, we can have a deep understanding to the molecular imprinting and recognition process. This work will regulate and control the thermodynamics, kinetics and related factors to improve the recognition performance of the novel material. In brief, this project aims to provide a theoretical support for the selective recognition bio-macromolecule， develop a new method to detect the amantins in blood with high precision， and build the foundation to efficiently clean the amantins from blood.

选择性识别生物大分子是分离分析及纯化、药物传递和医学诊断等多学科追求的目标。群体性蘑菇中毒时有发生致死率高，鹅膏毒肽是主要毒素。研制专一性捕获血液中鹅膏毒肽的人工受体，对患者的治疗康复具有重要意义。鹅膏毒肽稀缺昂贵是制备其印迹聚合物受体的主要障碍。受生物学配体与受体识别的启示，本项目拟开展：提炼鹅膏毒肽的关键作用位点，设计合成基于鹅膏毒肽识别决定区的系列模板，优化模板、功能单体及交联剂等的自组装，构建仿生识别鹅膏毒肽的新型表面印迹材料；解析模板、制备方法和制备条件等对印迹材料组成、结构和性能影响的内在关系；探明新材料分子识别机理，从分子水平深入认识印迹和识别过程；调控热力学和动力学等相关因素，提高新材料的专一性识别性能。项目的实施为选择性捕获及高灵敏准确检测血液中的鹅膏毒肽提供新方法，为高效捕获清除患者体内的鹅膏毒肽提供基础数据，为新型生物大分子人工受体的广泛研究提供理论技术支撑。

选择性识别生物大分子是分离分析及纯化、药物传递和医学诊断等多学科追求的目标。群体性蘑菇中毒时有发生致死率高，鹅膏毒肽是主要毒素。研制专一性捕获血液中鹅膏毒肽的人工受体，对患者的治疗康复具有重要意义。鹅膏毒肽稀缺昂贵是制备其印迹聚合物受体的主要障碍。.受生物学配体与受体识别的启示，本项目提炼鹅膏毒肽的关键作用位点，设计合成基于鹅膏毒肽识别决定区的模板分子，优化模板、功能单体及交联剂等的自组装，构建仿生识别鹅膏毒肽的新型硅胶表面印迹材料和多种表面印迹量子点；解析模板、制备方法和制备条件等对印迹材料组成、结构和性能影响的内在关系；探明新材料分子识别机理，从分子水平深入认识印迹和识别过程；调控热力学和动力学等相关因素，提高新材料的专一性识别性能。.利用识别决定区印迹策略，研制成功了硅小球表面印迹的鹅膏毒肽受体。该受体对对血清不同浓度的α-鹅膏毒肽的除去率都在90%以上；对β-鹅膏毒肽也有很好的吸附能力，其除去率都超过60%。成功研制了多种鹅膏毒肽识别决定区印迹量子点荧光传感器，实现血清中α-鹅膏毒肽的不经分离的快速高灵敏检测，检出限低至8ng/mL。.本研究的科学意义包括：1. 第一次制备了选择性鹅膏毒肽吸附剂，有可能用于蘑菇中毒患者体内主要毒素鹅膏毒肽的检测与清除；2 .解决不可能用直接鹅膏毒肽制备印迹鹅膏毒肽受体的难题;3.为新的生物大分子仿生受体的广泛研究提供了技术与理论支撑。