Transient Intermediates of Electron and Proton Transfer

在这个由化学部化学结构、动态和机制B项目资助的项目中，西雅图华盛顿大学化学系的Frantisek Turecek教授正在开发新的方法来研究涉及生物相关化合物（如蛋白质和DNA）的化学反应的瞬态中间体。当蛋白质和DNA受到损伤时，会产生离子或化学自由基等瞬时中间体。了解与电离和化学自由基损伤蛋白质和DNA相关的反应性中间体的化学过程、机制和性质，有助于开发改进的DNA和蛋白质保护和修复方法。该项目处于有机化学、物理化学和生物分析化学的交叉点，在为各级科学家提供全面教育方面有着良好的记录。这个研究小组欢迎目前或历史上在科学领域代表性不足的学生，并有能力提供最高水平的教育和培训。此外，该小组在国内和国际上积极促进与其他研究小组和研究所的合作。这项研究有三个主要目的。在Aim 1中，该小组结合了两种技术，气相电子转移和紫外光解作用光谱，以深入了解蛋白质和核酸生物反应的瞬态自由基中间体的电子结构。用有限大小的模型系统来研究这些生物分子，如肽和DNA片段，使它们适合于计算分析。目标2关注非共价生物分子复合物的结构和动力学。该方法将实验质谱研究与Born-Oppenheimer分子动力学计算相结合，可能会产生关于生物分子复合物中非共价键的特征和大小的有价值的信息。Aim 3利用一种新的合成偶联反应进行固相肽衍生化，并改进质谱分析，目的是实现未知肽的从头测序。

In this project funded by the Chemical Structure, Dynamic & Mechanism B Program of the Chemistry Division, Professor Frantisek Turecek of the Department of Chemistry at University of Washington, Seattle, is developing new methods of investigating transient intermediates of chemical reactions involving biologically relevant compounds such as proteins and DNA. Transient intermediates such as ions or chemical radicals occur when proteins and DNA are damaged. Understanding of the chemical processes, their mechanisms, and nature of reactive intermediates associated with ionization and chemical radical damage to proteins and DNA helps to develop improved means for DNA and protein protection and repair. The project lies at the interface of organic, physical, and bioanalytical chemistry, and has a proven record of providing all-round education to scientists at all levels. This research group welcomes students currently or historically underrepresented in science and is well-positioned to provide the highest level of education and training. In addition, the group is active both nation-wide and internationally in fostering collaborations with other research groups and institutes. The research consists of three main aims. In Aim 1, the group combines two techniques, gas-phase electron transfer and UV photodissociation action spectroscopy, to achieve insight into the electronic structure of transient radical intermediates of biological reactions of proteins and nucleic acids. Studying these biomolecules with model systems of limited size, such as peptides and DNA fragments, makes them amenable to computational analysis. Aim 2 concerns the structure and dynamics of non-covalent biomolecular complexes. The approach, which combines experimental mass spectrometry studies with Born-Oppenheimer molecular dynamics calculations, is likely to produce valuable information on the character and magnitude of non-covalent bonding in biomolecular complexes. Aim 3 utilizes a new synthetic coupling reaction for solid-phase peptide derivatization and improves mass-spectrometric analysis with the aim of achieving de novo sequencing of unknown peptides.