Probing the interactions between cisplatin and essential amino acids using electrospray ionization mass spectrometry

Abstract

Cisplatin (cis-[PtCl2(NH3)2]) is an important platinum-containing anticancer drug for treatment of solid malignancies. Probing the interactions between cisplatin and free amino acids are beneficial for investigation of its pharmacology and side effects. In this study, the interactions of twenty amino acids with cisplatin in water, acidic, neutral and basic solutions were studied using electrospray ionization mass spectrometry (ESI MS), respectively. Adducts of cisplatin and amino acids were recognized. It had been found that the reactions of cisplatin with amino acids depended on solution media and essential amino acids. Multiple tandem mass spectrometry was employed to probe the affinities of nucleophilic functional groups, such as side chains, α-NH2 groups and α-COOH groups on amino acids for cisplatin in water. The results indicated that the chelated complexes formed were stable in aqueous solution. For free Cys, Met and His, their side chains had higher affinities than α-NH2 groups. For free Ser, Thr, Asp, Glu, Asn and Gln amino acids, their α-NH2 groups had higher affinities than the side chains and α-COOH groups. For Lys, Arg, Phe, Tyr and Trp, platinum may coordinate to their aromatic rings of the side chains or α-NH2 groups. For other amino acids Gly, Ala, Val, Leu, Ile and Pro, their α-amino groups had higher affinities for cisplatin than α-COOH groups. These results provide the insights for understanding of the mechanism and side effects of cisplatin.