多肽和蛋白质诱导无机纳米粒子手性自组装的研究

Surface Plasmon enhanced chiral nanomaterials have attracted much attention, owing to their broad potential applications, particularly in bio-sensing, chiral selectivity, chiral recognition, non-linear optical materials, negative refractive index materials, chiral catalyst, etc. In this study, we will develop a facile method for the preparation of plasmonic chiral nanomaterials through the self-assembly of inorganic nanoparticles induced by polypeptides and proteins. The plasmonic enhancement of the inorganic part can transfer and magnify the weak circular dichroism signal of bio-macromolecules from far-UV to vis-NIR region. This study will pave the new way for the unitization of chiral nanomaterials for biological applications, such as the study of secondary structures of polypeptides in vivo or in cells. We will also develop an approach for the analysis of folding structures of intrinsic disordered proteins and their Pathogenesis mechanism in vivo. On the other hand, we will use FDTD simulation based on the experimental result to understand the mechanism of surface plasmon enhancement of the CD signals. This will allow us to predict and design chiral nanomaterials with giant anisotropic factors.

手性纳米结构由于其独特的光学性质，将会在生物传感、分子检测、非线性光学、负折射率材料、手性催化等诸多领域具有广泛的应用前景。本项目将设计利用天然多肽和蛋白质自身的手性结构，诱导和构筑表面等离子体纳米粒子的手性组装体，通过表面等离子体偶合效应实现多肽和蛋白质圆二色信号在可见-近红外区域的放大和增强；实验与理论模拟相结合，阐明纳米粒子手性光学的来源及增强机理，从而设计并构筑具有高各向异性手性系数（g-factor）的手性纳米材料；同时，通过蛋白质融合，构建天然无序蛋白的折叠方式和构象变化的检测平台，揭示其与伴侣分子作用前后无序区结构变化及生理学功能之关系，初步探索利用表面等离子体增强圆二色光谱研究淀粉样蛋白诱导细胞凋亡的机制。

如何利用天然手性生物大分子与纳米粒子在尺寸上的匹配性，精准调空纳米粒子之间的三维有序结构,从而构筑具有高各向异性手性系数的手性材料，并实现其圆二色信号在可见-近红外区域的放大和增强，是手性纳米材料领域中的重要科学问题。我们推导出了更加直观的g-factor计算公式，阐明了手性组装结构与共振波长的圆偏振光的匹配性，及手性结构的长程有序性，是实现大g-factor的决定性因素。以此为指导，设计并发展了一系列利用短肽GHS寡聚体、人胰岛淀粉样多肽（hIAPP）、人与动物的多种血清蛋白（SA）和手性聚合物等分别诱导和构筑金纳米粒子三维手性结构的方法；研究了生物有机分子的CD信号通过纳米粒子手性光学在可见-近红外区域的放大和增强的机理，利用聚合物配体与纳米粒子尺寸的匹配性，获得了具有高g-factor（0.12）的纳米粒子手性组装结构,并将其用于血清和胰腺器官中药物筛选方面的应用，在纳米粒子手性材料的应用方面取得重要突破。期间，共发表SCI论文17篇，待发表两篇，其中包括CCS Chemistry1篇。通过本项目的实施，培养高水平研究生5名。