Cisplatin binding to proteins: A structural perspective

The interactions of clinically established anticancer Pt-based drugs with proteins play crucial roles in Pt cellular uptake and biodistribution, as well as in determining side effects and resistance, thus affecting the overall pharmacological profile of this class of drugs. Here, we summarize a number of recent crystallographic studies of cisplatin/protein adducts that contribute unveiling the molecular basis for cisplatin-protein recognition. Details of each molecular structure are carefully and comparatively described; common trends and regularities occurring in the analyzed adducts are highlighted. Analysis of the structural features of its protein derivatives, integrated with selected results arising from the application of other biophysical methods on strictly related systems, allows an overall elucidation of the protein platination process and offers a more comprehensive understanding of the mode of action of cisplatin and its parent Pt-based drug