Reaction of cisplatin analogs with selenomethionine

Rebekkah Lively and Kevin M. Williams

Analogs of the platinum anticancer compound cisplatin have been reacted with the nonstandard amino acid selenomethionine (SeMet). SeMet was found to react faster than methionine (Met) with a representative platinum complex; 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. Thus, while only a subset of proteins have selenium-containing amino acids, platinum complexes could target them kinetically. Additionally, the presence of SeMet was found to greatly increase the rate of displacement of trans ligands on the platinum.