Surface Electrochemistry of DNA Conformational Switches

拟议的研究的主要目标是获得功能脱氧核糖核酸（DNA）的表面电化学的透彻的知识。DNA作为遗传信息的载体，在生物学中起着举足轻重的作用，了解DNA的性质至关重要。除了典型的单链和双螺旋，复杂的DNA纳米结构（所谓的DNA构象开关）可以被构建为具有所需的功能或反应性。使用标准的生物化学测定，已经发现溶液中完美的双螺旋和适当设计的DNA开关有效地介导电荷流动。然而，当它们结合到电极表面时，这不是共识机制;在这种情况下，DNA介导的和直接的电子转移都得到了实验观察的支持。 这项研究将有助于我们理解DNA和DNA纳米结构中的结构-传导相关性。它也对应用有直接影响：阐明表面结合的DNA开关中的确切电荷传输途径对于开发灵敏的电子生物传感器（例如，用于监测血液中的疾病生物标志物）。 我们将首先专注于电极结合的DNA开关的设计和标记策略。将进行结构和电化学相结合的研究，以区分这些DNA纳米结构中的替代传导途径，并定量评估电子转移动力学。这项研究的下一阶段将包括对信号开关（电荷传导）机制及其结构基础的全面研究，包括实时光谱和显微镜测量以及固态实验。

The main goal of the proposed research is to obtain a thorough knowledge of the surface electrochemistry of functional deoxyribonucleic acids (DNA). It is essential to understand the nature of DNA which plays a pivotal role in biology as the carrier of genetic information. Besides typical single strands and double helices, complex DNA nanostructures (so-called DNA conformational switches) can be constructed to have desired functions or reactivities. Using standard biochemical assays, perfect double helices and properly designed DNA switches in solution have been found to efficiently mediate charge flow. However, this is not the consensus mechanism when they are bound to an electrode surface; in that case both DNA-mediated and direct electron transfer are supported by experimental observations. The proposed research will help us to understand structure-conduction correlations in DNA and DNA nanostructures. It also has direct impact on applications: elucidation of the exact charge transport pathway in surface-bound DNA switches is crucial for the development of sensitive electronic biosensors (e.g., for monitoring disease biomarkers in blood). We will initially focus on design and labeling strategies for electrode-bound DNA switches. Combined structural and electrochemical studies will be carried out to discriminate between alternative conduction pathways in these DNA nanostructures and to quantitatively evaluate the electron transfer kinetics. The next phase of this research will comprise a comprehensive study of the signal-switching (charge conduction) mechanism and its structural basis, including real-time spectroscopic and microscopic measurements as well as solid-state experiments.