Cisplatin is the most widely used chemotherapeutic agent for the treatment of the majority of solid tumors, and the resistance of neoplastic cells to this cytotoxic compound poses a major problem in clinical oncology.

In this study, cisplatin was reacted in solution with the dipeptide cysteinyl-glycine (CysGly), chosen as a functional model of glutathione, and the reaction products were analyzed by electrospray ionization mass spectrometry (ESI-MS). ). Selected complexes were subjected to multiple photon dissociation IR spectroscopy (IRMPD) to obtain their vibrational characteristics. Experimental IR ion spectra were compared to calculated IR absorptions of different plausible isomer families, revealing that CysGly preferentially binds platinum(II) via its deprotonated thiolic group in the monovalent cis-[PtCl(NH3)2) complex. (CysGly)]+, and to evolve in the chelate structure linked to the S,N cis-[PtCl(NH3)(CysGly)]+ via the SH and NH2 functionalities of the cysteine ​​residue. Furthermore, the results indicate that the platination reaction does not affect the CysGly peptide bond, which remains in its trans configuration.

These results therefore provide additional information on the reactivity of Pt(II) complexes with glutathione, involved in cellular resistance to cisplatin.IRMPD 5bc8b

Learn more: DOI: 10.1016/j.jinorgbio.2023.112342

Platform: FT-ICR, ICP - CNRS/Université Paris Saclay, Orsay