Cisplatin (cis-DDP) and its cis-coordinated analogues, carboplatin and oxaliplatin, have been successfully used in the treatment of testicular and other solid tumors, but applications are restricted by side effects and intrinsic and acquired resistances. [1][2][3] The discovery of trans-coordinated platinum complexes with antitumor activity provides a novel approach for cancer chemotherapy. [4,5] Among several types of transplatinum complexes, trans-[PtCl 2 {E-HN=C(OCH 3 )CH 3 } 2 ] (trans-EE) raised particular interest because of its higher cytotoxicity than the cis isomer and its activity towards several cis-DDP-resistant tumor cells. [4] Mechanistic studies indicated that trans-EE has different DNA binding modes relative to cis-DDP, [6,7] although their reaction rates were similar. [8] DNA modified by trans-EE could not be recognized by high-mobility group (HMG), the protein that interferes with DNA repair of cis-DDP adducts, whereas histone H1 could bind to trans-EE-modified DNA and prevent DNA polymerization and repair. [9] A recent study also indicated that methionine was the preferable binding site of trans-EE in the reaction with cytochrome c, and different binding modes were observed between cis-and trans-platinum complexes. [10] Many cellular molecules, including proteins, peptides, and also some small molecules, can play significant roles in the functioning of and resistance to drugs, such as DNA platination, drug transport, and efflux. [2,11,12] Sulfur-containing proteins are of special interest because of their high affinity for platinum, their abundance (e.g. albumin), [13,14] and their involvement in metal-ion transport (e.g. the copper transporter protein CTR1, which contains methionine-rich extrac-Scheme 1. Kinetic pathway for the formation of trans-EE adducts.