Transient Intermediates of Electron and Proton Transfer

在化学部化学结构、动力学机制B计划资助的这个项目中，西雅图华盛顿大学化学系的Frantisek Turecek教授正在开发研究涉及生物相关化合物如蛋白质和DNA的化学反应的瞬时中间体的新方法。 当蛋白质和DNA被破坏时，会出现离子或化学自由基等瞬态中间产物。 了解与蛋白质和DNA的电离和化学自由基损伤相关的化学过程、其机制以及反应中间体的性质，有助于开发改进的DNA和蛋白质保护和修复方法。 该项目位于有机，物理和生物分析化学的接口，并已证明为各级科学家提供全方位教育的记录。该研究小组欢迎学生目前或历史上在科学代表性不足，并有能力提供最高水平的教育和培训。 此外，该小组在全国和国际上积极促进与其他研究小组和机构的合作。研究包括三个主要目标。在目标1中，该小组结合了两种技术，气相电子转移和紫外光解离作用光谱，以实现对蛋白质和核酸生物反应的瞬时自由基中间体的电子结构的洞察。用有限大小的模型系统研究这些生物分子，如肽和DNA片段，使它们适合于计算分析。目的2：研究非共价生物分子复合物的结构和动力学。该方法结合了实验质谱研究与玻恩-奥本海默分子动力学计算，很可能产生有价值的信息的字符和大小的非共价键合的生物分子复合物。目的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.