两亲性蛋白质修饰纳米酶的构效关系及其在酶级联反应中的应用研究

Construction of efficient and stable mimic enzyme is one of the research objectives of chemistry and biology. As a novel artificial enzyme, the catalytic activity of inorganic nanomaterial with enzyme-like characteristics (nanozymes) is significantly superior to traditional artificial enzymes. Furthermore, nanozymes possess unique physicochemical and mechanical properties. Thus, nanozymes have become an increasingly hot topic and focus of interdisciplinary research. However, in practice, nanozymes still face some bottlenecks, such as how to further improve the catalytic activity, enhanced particle stability and biocompatibility. This project intends to design and synthesis of a new type of nanozymes modified with amphiphilic proteins. A combination of the catalytic active center and the hydrophobic microenvironment provided by the proteins on the scaffold of nanozymes leads to the fabrication of high efficient, stable, and biocompatible nanozymes. The enzyme catalytic activity of nanozymes was regulated by using different structured proteins and physicochemical factors. The relationship of structures, properties and functions of amphiphilic proteins modified nanozymes was investigated. The binding mechanism between the nanozyme and substrate, as well as the catalytic mechanism were revealed in molecular level, which provides new research ideas for the design and synthesis of new and efficient artificial enzymes. Furthermore, the nature enzyme was immobilized on amphiphilic proteins modified magnetic nanozymes to fabricate enzyme cascade systems via self-assembly methods. It is expected to clarify the inherent correlation between the function of the enzyme cascade system and the structure of the amphiphilic proteins modified nanozymes. This will provide convenient and facile ways for the development of reusable enzyme cascade systems with high activity and stability, thus enriching the nanozyme research and broadening its practical applications.

无机纳米模拟酶(纳米酶)是一类新型的人工模拟酶，既具有明显优越于传统模拟酶的催化活性，又兼具独特的物理化学特性。本项目拟构建高效、稳定、生物相容的两亲性蛋白质分子修饰的纳米酶，集纳米酶的催化中心和两亲分子所提供的亲疏水微环境于一体。通过不同的两亲性蛋白质分子结构和物理化学因素调控纳米酶的选择性结合能力和催化性能，研究修饰纳米酶的结构－性质－功能之间的关系，在分子水平揭示修饰纳米酶与底物的结合及催化机制，为理性构建新型高效稳定模拟酶提出新的研究思路。在此基础上，利用两亲性蛋白质分子修饰的磁性纳米酶为载体，以自组装方式包载天然酶构筑酶级联反应系统，探索修饰纳米酶与天然酶的相互作用，明确修饰纳米酶的结构特性与酶级联反应系统功能的内在联系，为高活性、稳定和便于回收的酶级联反应系统提供新颖便捷的构建途径，从而丰富纳米酶学的研究内容，拓展纳米酶在生物医学、食品、环境检测与治理等诸多领域的应用空间。

纳米酶是具有类似生物酶催化功能的纳米材料，构建高效纳米酶并研究其催化机制对于其实际应用具有重要意义。本项目重点研究了两亲性蛋白质和氨基酸分子修饰的贵金属和金属氧化物纳米酶，及其与石墨烯复合纳米材料的类模拟酶性质。系统深入地研究了环境因素对纳米酶的类模拟酶活性的调控作用及作用机制，包括金属离子、卤素离子、含硫无机阴离子和有机小分子等。探讨这些无机离子和有机小分子与纳米酶的界面相互作用对纳米酶的类酶活性的影响，阐述纳米酶表界面结构和物化性质对类酶催化的影响规律。在此基础上，基于纳米酶构建人工集成酶(IAEC)平台，通过合理化设计和精细化控制纳米酶的微纳结构保证了纳米酶与天然酶复合体中酶的活性和酶之间的协同作用及底物的快速传递，并对IAEC平台的催化性能与复合纳米酶的构效关系进行了分子层次探讨，为IAEC平台的理性设计及可控构建提供了依据，拓展了纳米酶在临床医学的应用空间。