Reactions of Cisplatin Analogs with Selenomethionine

Cisplatin is a well-known anti-cancer drug that is effective, but also has some severe and unwanted side effects. Analogs of cisplatin were reacted with the nonstandard amino acid selenomethionine (SeMet), and the products were characterized by 1H and 195Pt NMR spectroscopy and HPLC. In previous studies, SeMet was found to react faster than methionine (Met) with a representative platinum complex (Pt(dien)Cl2), therefore SeMet is said to react faster kinetically. Thus, while only a subset of proteins have selenium-containing amino acids, platinum complexes could target them kinetically. Cisplatin analogs with two leaving groups have also been studied. Pt(Me4en)(NO3)2 (Me4en = N,N,N’,N’-tetramethylethylenediamine) reacts with SeMet to form a [Pt(Me4en)(SeMet-Se,N)]+ chelate regardless of the Pt:SeMet ratio. Pt(en)(NO3)2 (en = ethylenediammine) reacts to form three possible products, with the distribution dependent on the Pt:SeMet ratio and time