Transient Intermediates of Electron and Proton Transfer

University Of Washington, Seattle WA

Investigators

Abstract

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.