Interaction between Platinum Complexes and a Methionine Motif Found in Copper Transport Proteins

摘要

Cisplatin (cis-[PtCl2(NH3)2], cis-DDP) and other platinum complexes used in anticancer therapy, such as carboplatin and oxaliplatin, are able to cross the cell plasma membrane and eventually reach the nucleus, where they form adducts with DNA that are at the basis of their antitumor activity. Early studies suggested that cis-DDP enters the cell mainly by passive diffusion. However, more recently, a growing body of evidence has revealed an alternative route for cis-DDP uptake involving the high-affinity copper transporter Ctrl, a permease located on the plasma membrane and constituted by three transmembrane helices, an extracellular N-terminal domain, and a cytosolic C-terminal domain.