Transient Intermediates of Electron and Proton Transfer

在这个由化学系化学结构、动态和机制B计划资助的项目中，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)的化学反应的瞬时中间产物。当蛋白质和DNA受损时，会产生离子或化学自由基等瞬时中间体。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、它们的机制和活性中间体的性质有助于开发改进的DNA和蛋白质保护和修复手段。该项目位于有机、物理和生物分析化学的交界处，并有为各级科学家提供全面教育的可靠记录。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，并处于有利地位，能够提供最高水平的教育和培训。此外，该小组还在全国和国际范围内积极促进与其他研究小组和研究所的合作。本研究由三个主要目的组成。在目标1中，该小组结合了两种技术，即气相电子转移和紫外光解离作用光谱，以深入了解蛋白质和核酸生物反应的瞬时自由基中间体的电子结构。用有限大小的模型系统，如多肽和DNA片段来研究这些生物分子，使它们易于计算分析。目的2涉及非共价生物分子络合物的结构和动力学。该方法将实验质谱学研究与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体中非共价键的性质和大小的有价值的信息。目的3利用一种新的合成偶联反应进行固相多肽衍生化，并改进了质谱分析，以实现未知多肽的从头测序。

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.