Interaction of mental complexes with biomolecules

Research project P 14290 Interaction of metal complexes with biomolecules B.K. KEPPLER 08.05.2000Platinum complexes like cisplatin or carboplatin are established antitumor drugs. Also some ruthenium complexes show promising antitumor activity in clinically relevant tumor models. The knowledge of the interaction of these metal complexes with biologically occuring targets like peptides or nucleotides is of great importance to understand the mode of action of this class of antitumor agents. We intend to investigate the reactions of platinum and ruthenium compounds developed in our laboratory with DNA fragments at the molecular level by means of HPLC-ESI-MS and CE-ESIMS. Especially the coupling of capillary electrophoresis (CE) with a mass spectrometer as detection system offers new possibilities in analytical separation and characterization of the reaction products. Beside mono- and oligonucleotides, especially sulfur containing peptides are important targets for the metal complexes. They seem to play an important role in the field of drug resistance and activation of the drugs and will also be subject of intensive studies. The obtained results might lead to a better understanding how the different metal complexes work and might enable us to synthesize new, optimized antitumor active compounds.