Interactions of anticancer Pt compounds with proteins: an overlooked topic in medicinal inorganic chemistry?

A critical discussion is presented about the possible role of Pt–protein interactions in the mechanisms of action of platinum anticancer compounds. Although, since 40 years from its discovery, cisplatin and analogues are believed to exert their therapeutic effects via direct interactions with nucleic acids, several proteins/enzymes have recently appeared to be involved in the compounds' overall pharmacological and toxicological profiles, apart from classical serum transport proteins and metal detoxification systems. As an example, the emerging role of zinc finger proteins is noteworthy in the activity of platinum drugs. Moreover, the pursuit of novel platinum candidates that selectively target enzymes is now the subject of intense investigation in medicinal bioinorganic chemistry and chemical biology. An overview is presented of the most representative studies in the field, with particular focus on the characterization of the Pt–protein interactions at a molecular level, using different biophysical and analytical methods.