Reaction of cisplatin analogs with selenomethionine

Rebekkah Lively, Stephen C. Chmely, and Kevin M. Williams

Analogs of the platinum anticancer compound cisplatin have been reacted with the nonstandard amino acid selenomethionine (SeMet) and characterized by NMR spectroscopy. SeMet was found to react faster than methionine (Met) with a representative platinum complex containing only one coordination site ([Pt(dien)Cl]Cl); however, over time, equal amounts of the SeMet and Met products were observed. Thus, both SeMet and Met products have similar thermodynamic stabilities, but SeMet is kinetically faster to react. Platinum complexes with a chelated diamine ligand and two leaving groups have also been studied to obtain insights about the trans effect caused by selenomethionine. Displacement of the diamine ligand can occur when two Se-coordinated SeMet residues are present but not when one SeMet is chelated via the Se and N atoms.