以螺旋高分子为骨架的仿生酶研究

This proposal will focus on the design of artificial enzymes based on helical polymers and investigate the enzymatic nature of these mimics in catalysis. By taking advantage of the deveplopment of foldamer chemistry, the well-studied aromatic amide foldamers were employed as scaffolds to develop artificial enzymes. In particular, two kinds of enzymes including hydrolases and glutathione peroxidases were simulated. To study the relationships between helical structure and catalytic activity, the artificial enzymes were rationally altered in terms of helix lengths, conformations, helical handedness as well as the catalytic microenvironment. These studies will provide new insights in the enzymatic machenism in catalysis. In order to discovery the general roles of helical structures for enzyme catalysis, we try to obtain the information from the exploration of two biomimetic enzyme systems which is useful for the design of highly efficient enzyme mimics by using helical scaffolds. Moreover, the single-handed helical enzyme mimics are extremely interesting and specific, and they are able to be left-handed or right-handed. Obviously, these mimics should be much better than ones composed of DNA scaffolds and have great potential in the applications of chiral catalysis. Behind this proposal, a deep understanding on the structure-function relationships during enzyme catalysis might be presented, and the promising chiral catalysts would be designed for the important industrial and biomedical applications as well.

本课题将报道螺旋高分子人工酶的设计及其酶学性质研究。利用人造折叠体发展的平台，选用已经研究成熟的芳香酰胺类螺旋分子作为骨架，构建两种不同的人工酶：水解酶模型和谷胱甘肽过氧化物酶模型。通过调节螺旋分子的长度、构象、螺旋手性以及人工酶的催化部位环境，研究螺旋高级结构与催化活性的关系，加深对天然酶催化机制的理解。多酶体系的应用，有利于研究螺旋高级结构在催化领域的一般性规律，为未来设计更高效的酶模型提供重要的基础信息。此外，我们还设计了单一螺旋手性的仿生酶。这些具有单一左手螺旋或单一右手螺旋的仿生酶在结构上是独特的，它们有潜力和优势替代DNA模板催化剂，并应用到手性催化反应领域。通过本课题的研究，阐明酶催化过程中螺旋结构与功能的本质关系，发展有重要应用前景的高效手性催化剂。

为了构筑螺旋高分子仿生酶，本项目发展了芳香酰胺类螺旋高分子以及自折叠螺旋高分子体系。针对以芳香酰胺类螺旋高分子为骨架构筑人工酶的设计方案，我们合成了制备螺旋高分子所需的具有不同结构特征的单体库。利用不同的单体，通过类似肽合成的方法制备了不同链长的寡聚物和聚合物，并将催化功能基团引入到螺旋结构中获得了两类酶模型体系。为了理解分子手性到螺旋手性的放大规律，我们系统研究了手性碳原子如何诱导螺旋手性的机制，发现了在同序列分子结构中螺旋长度变化会引起螺旋手性反转的新现象。通过手性基团的诱导控制，我们能够控制螺旋高分子人工酶在催化过程中的空间选择性。除了芳香酰胺类螺旋高分子外，我们利用螺旋密码子的设计想法发展了特色的自折叠螺旋高分子体系。自主设计的自折叠螺旋高分子体系制备简单，解决了螺旋高分子领域中刚性螺旋高分子模板合成困难的问题。芳香共轭螺旋高分子的成功制备首次实现了单根螺旋高分子的STM成像。自折叠螺旋高分子的中空手性孔道不仅可以实现分子识别与跨膜传输，其具有类似天然酶的独特微环境，可以有效实现催化作用。为了更容易制备螺旋高分子模板，我们设计了自折叠动态共价螺旋高分子体系，实现了孔道内选择性催化作用。本研究建立的芳香酰胺类螺旋高分子以及自折叠螺旋高分子体系有望在分子识别、物质传输、仿生酶催化、超分子组装、手性分离和含孔膜材料等领域展现独具特色的应用前景。