The main purpose of the project is to understand the mechanism of sensitization of DNA damage process as well as to develop methods of designing new sensitizers. This aim will be achieved by creating an interdisciplinary (chemically-biological) laboratory that enables such substances to be designed rationally. We assume a strong synergy to appear due to a positive feedback between particular tasks realized in various domains such as: computational chemistry, chemical synthesis, analytical chemistry, radiation chemistry, photochemistry, molecular biology and biology of the cell. Thus, we approach the problem of new sensitizers in a systemic manner. The theoretically proposed compound will be scrutinized experimentally after its incorporation into the DNA molecule and only then will it be tested in the cell.
The results of the project will contribute to our understanding of the mechanisms governing ionizing radiation/UV induced damage to labeled DNA. By completing the planned investigations, we will gain basic knowledge about the processes induced in DNA by radicals, as well as those under complex cellular conditions where DNA damage triggers a cascade of enzymatic reactions related to DNA repair or cell death. This information will be important for the design of other types of DNA damage sensitizers or chemotherapeutics. Finally, completion of the project will result in a series of compounds which could be employed in future anticancer therapies. In light of the small number of radio- and photosensitizers used in clinics, it is difficult to overestimate the access to compounds with sensitizing activity confirmed at the cellular level.