基于多肽的共组装结构与生物活性研究

Currently, nanostructures with different morphologies and dimensions have been constructed using peptides; however, the research and development of their bioactivities are still in its infancy stage. The finding of high catalytic performance of nanoclusters (NCs) has opened a new avenue for studying enzyme mimics, however, the issue of substrate’s specificity need to be solved urgently. If NCs and peptides can be co-assembled into one nanostructure, in principle, it holds great potential to build up de novo nanostructures with novel bioactivities. This project will deeply figure out the molecular mechanism of natural bioactive centers, and in combination with NCs and functional molecules, to develop a technique for co-assembling, and build up de novo nanostructures with bioactivities; we will deeply investigate the dynamic formation procedure and molecular mechanism of peptide-based co-assembles under different conditions such as in solutions, on the interfaces between solids and liquids or gases, build up novel crystallization approaches for peptide-based co-assembles, and then with the help of synchrotron radiation X-ray diffraction, this project aims to analyze the structures of peptide co-assembles with high resolutions, and obtain the binding sites between different components inside co-assembles; Finally, we will verify the biological activities of so-built peptide co-assembles, and demonstrate their potential and valuable applications in biomedical fields. The results from this project will not only enrich current techniques for bio-nano interdisciplinary researches, but also hold potential to open new routes for studying de novo bioactive nanostructures.

目前，利用多肽已经能组装出不同空间形状的纳米结构，然而，其生物活性的开发却仍处于初级研究阶段。纳米晶簇的高效催化性能的发现为仿酶的研究开辟了新方向，然而，其对底物的选择特异性问题仍亟待解决。如果能将纳米晶簇与多肽进行共组装，原则上有望创造出具备新型生物活性的人工纳米结构。本项目拟通过深挖天然生物活性中心的分子机制，结合纳米晶簇与功能分子，开发出一种基于多肽的共组装技术，构造出具备新型生物活性的人工纳米结构；深入研究多肽共组装结构在溶液中、固液/气界面等条件下，结晶的动态过程及分子机制，建立新的多肽共组装结构的结晶方法；进而利用同步辐射X射线衍射法，对多肽共组装结构进行高分辨解析，并获取其组装单元间的结合位点；最后，我们将验证所制备的多肽共组装结构的生物活性，及其在生物医学中的潜在应用价值。此项目的研究结果不仅将丰富当前的生物纳米交叉研究技术，而且还有望为人工结构与生物活性的研究开辟新途径。

本项目通过研究天然生物活性中心的分子机制，开发基于多肽的共组装技术，构建具备新型独特生物活性的人工纳米结构。利用含有酪氨酸的短肽在氧化条件下形成稳定的二聚体结构，进而引起了较高的量子产率和光谱红移。并且体外突变的方法可以证明氨基酸和它们的序列在调节荧光中发挥重要作用。这种荧光纳米结构具有分级组装的特性，有利于光活性的调节。同时发现短肽与生物分子多巴胺的共组装可以有效抑制氧化交联形成黑色素，这表明氧化在仿生合成荧光纳米结构中具有重要作用。另外，我们对具有生物活性的肽序列进行改造和组装合成了新型肽基自组装纳米颗粒，在抗菌消炎、降脂及抑制痤疮等方面具有良好的效果，发掘了其在生物医学领域的应用潜力。发表了10余篇SCI论文，资助培养了1名博士后及3名硕士研究生，达到了预期目标。通过本项目的研究，在多肽自组装、功能分子与生物分子的共组装及活体动物实验等方面积累了丰富的研究经验，在此基础上我们将继续深入研究，以期在生命科学领域取得新成果。