Using NMR spectroscopy for improvement of cisplatin-based drugs

One of the aims of the present research is the development of new anticancer drugs by modifying the already known ones to increase their cytostatic activity while lowering the side-effects. The major goal of this project is to investigate the sequence selectivity of cisplatin-DNA interaction in order to understand the biochemical mechanism of cisplatin effect and consider the way to reduce its toxicity. To achieve this goal, we employed modern NMR methods, taking so the advantage of the fact that it is possible to study the biological compounds of interest in solution under nearly physiological conditions. In my contribution, I will show the structural properties of DNA 22-mer containing T4-loop crosslinked with cisplatin derivative RR-DACH. NMR data acquisition and processing as well as the determination of the structural models using molecular dynamics simulations will be presented.