Oxidation of DNA-bound peptides and proteins by DNA-mediated electron transfer reactions

• Applicant: Professor Dr. Hans-Achim Wagenknecht
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2000 to 2001
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5252952

DNA charge transport chemistry has been the subject of considerable interest with possible consequences in areas as diverse as mutagenesis and molecular electronics. The goal of this project was to put DNA-mediated charge transfer processes in a biological context. In this project, two different approaches were made to investigate how peptides and proteins influence or modulate charge transfer processes through the DNA. In the first part, small DNA-binding peptides were tethered convalently to the 5`-terminus of oligonucleotides. Charge transfer processes were photoinitiated by an intercalating ruthenium photooxidant using the flash-quench technique. In the second part, charge transport and radical trapping were examined in DNA assemblies in the presence of site-specifically bound DNA-interacting enzymes such as cytosin methyltransferase "Hhal" mutants and alkyladenine glycosylase. Charge migration through the DNA base stack has been probed both spectroscopically to observe the formation of radical intermediates and biochemically to assess irreversible oxidative DNA damage. Protein-dependent DNA charge transport is observed over 50 A with guanine radicals. Given the time scale and distance regime such protein-dependent DNA charge transport chemistry requires consideration physiologically.

• DFG Programme: Emmy Noether International Fellowships