蛋白质的掺杂及其构象变化特征与电子传输特性

Electron transport (ETp) in proteins (including enzymes) refers to such a process that electrons are carried across the entire protein molecule. It plays a key role in many biological processes, such as respiration, photosynthesis, and various metabolic cycles. Furthermore, ETp of proteins is also of great interest in the fields of bioelectrocatalysis, bioelectronics, and more recently, nanobiotechnologies. However, how to achieve, and further to enhance the ETp properties of proteins at their native conformations is an important fundamental issue, which is still remained to be unsolved. This project proposes a new concept, which is based on the protein doping, to achieve the high ETp properties of the proteins and keep their native conformations at the same time, and to elucidate the correlation of the doping-induced conformation changes of the proteins and their ETp characteristics. This project selects three different types of proteins, namely horadish peroxidase (HRP, a representative of heme iron-containing redox enzyme), human serum albumin (HSA, is the most abundant protein in the circulatory system, constituting nearly 52–60% of plasma, and is responsible for the binding and transport of a wide variety of amino acids, drug molecules, fatty acids, and metabolities to their molecular targets), and prion (PrP, an infectious agent thought to be the cause of the transmissible spongiform encephalopathies. The unfolding of its conformation can cause many neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Creutzfeldt-Jakob disease, amyloid disease, and many other abnormalities) for its study. Using electrochemical approaches in combination with spectroscopic techniques and theoretical calculations to study and develop the methods for enhancing the ETp properties of the proteins by doping approaches; to study the doping-induced conformation change features of the proteins and their ETp characteristics; to study the effects of the surface features of the conducts (substrates) on the conformation change features of the proteins and their ETp characteristics; to the correlation between the morphologies of the doped proteins and conformation change features of the proteins and their ETp characteristics. The results obtained from the study of the project are significance in developing the novel bioelectronic devices using the proteins as electron transport materials, and achieving the electron control in the molecular level.

蛋白质(酶)的电子传输(ETp)是指电子通过整体蛋白质的过程，它不仅在呼吸作用、光合作用、各种代谢循环过程中起重要作用，而且与生物电子学、生物电催化及纳米生物技术等领域密切相关，但如何实现蛋白质ETp并保持原有的构象仍是一个未解决的基础性问题。本项目提出通过对蛋白质的掺杂提高其ETp性能并阐明掺杂蛋白质的构象变化与ETp特性的关系。以辣根过氧化物酶、人血清白蛋白及朊蛋白为研究对象，以电化学方法为手段，结合光谱技术和理论计算，研究并建立通过对蛋白质掺杂提高其ETp性能的方法；研究掺杂分子对蛋白质构象变化特征、ETp特性的影响及机制；研究导体表面特性对掺杂蛋白质构象及ETp特性的影响；研究掺杂蛋白质在导体表面的形貌特征与其构象变化及ETp特性的关系。这些研究不仅有助于理解生命体系中蛋白质ETp机制，还可为构建以蛋白质为电子传输材料的特殊功能分子器件、实现在分子尺寸范围对电子的控制提供理论基础。

蛋白质(酶)的电子传输(ETp)是指电子通过整体蛋白质的过程，它不仅在呼吸作用、光合作用、各种代谢循环过程中起重要作用，而且与生物电子学、生物电催化及纳米生物技术等领域密切相关。但如何实现蛋白质ETp并保持原有的构象仍是一个未解决的基础性问题。. 本项目研究通过对蛋白质的掺杂提高其ETp性能，并阐明掺杂蛋白质的构象变化与ETp特性的关系。以电化学方法为手段，结合光谱技术和理论计算，研究了几类重要小分子，如Zn-酞箐衍生物（ZnPCs）、抗癌类药物FU、Vb12、血红素（Heme）、茶碱（TPY）以及一些具有共轭结构的大环分子对蛋白质HSA的掺杂及其方法；研究了这些掺杂分子对蛋白质构象的影响及其变化特征、对HSA的ETp性能的影响及机制、以及对HSA的ETp的能级的影响及其机制；研究了掺杂蛋白质在导体表面的形貌特征与其构象变化及ETp特性的关系。. 通过这些研究，我们发现这些外源小分子都能与HSA进行有效的掺杂，结合于HSA的IIA域，并位于Trp213氨基酸附近，进而影响Trp213的荧光性能，因此可以通过监控Trp213的荧光强度的变化判断外源分子对HSA的掺杂。这些分子对HSA蛋白质的构象影响不大，掺杂后HSA的构象仍以α螺旋构象为主，约为67%。具有共轭结构的分子能使HSA的ETp性能提高，并改变HSA的ETp的导带（CB）和价带（VB）的能级高度，但不同的掺杂分子可能导致CB和VB向不同的方向移动，因此可以选择不同的分子对蛋白质进行掺杂，使蛋白质的ETp带隙降低到所期望的值。掺杂后的HSA在电极或基底表面的固定可能会影响其构象，但我们发现如通过电极表面与蛋白质分子之间的–COOH和–NH2形成的酰胺键，或通过HSA分子内的Cys34游离的–SH基与基底表面的金形成Au–S键将HSA固定在基底表面，蛋白质的构象能得到较好的保持。. 这些研究成果发表论文SCI论文21篇，申请国家发明专利12件（已有8件获得授权）。. 这些研究不仅有助于理解生命体系中蛋白质ETp机制，还可为构建以蛋白质为电子传输材料的特殊功能分子器件、实现在分子尺寸范围对电子的控制提供理论基础。