Exploring metallodrug-protein interactions by mass spectrometry: comparisons between platinum coordination complexes and an organometallic ruthenium compound

Electrospray ionisation mass spectrometry was used to analyze the reactions of metal compds. with mixts. of selected proteins. Three representative medicinally relevant compds., cisplatin, transplatin and the organometallic ruthenium compd. RAPTA-C, were reacted with a pool of three proteins, ubiquitin, cytochrome c and superoxide dismutase, and the reaction products were analyzed using high-resoln. mass spectrometry. Highly informative electrospray ionisation mass spectra were acquired following careful optimization of the exptl. conditions. The formation of metal-protein adducts was clearly obsd. for the three proteins. In addn., valuable information was obtained on the nature of the protein-bound metallofragments, on their distribution among the three different proteins and on the binding kinetics. The platinum compds. were less reactive and considerably less selective in protein binding than RAPTA-C, which showed a high affinity towards ubiquitin and cytochrome c, but not superoxide dismutase. In addn., competition studies between cisplatin and RAPTA-C showed that the two metallodrugs have affinities for the same amino acid residues on protein binding.