The role of carrier ligands of platinum(ii) anticancer complexes in the protein recognition of Pt–DNA adducts

Abstract

In order to systematically investigate the influence of carrier ligands on the interaction of Pt–DNA adducts with damage recognition proteins, a series of DNA probes containing 1,2-GG platinum compound crosslinks using cisplatin, oxaliplatin, (S,S-DACH)PtCl₂ and (cis-1,4-DACH)PtCl₂ (kiteplatin) has been constructed. These complexes share similar DNA binding properties although they exhibit quite different cytotoxicity. It is revealed that HMGB1 (high-mobility group protein B1) was the most commonly found protein that recognizes all Pt(II)-DNA probes and prefers cisplatin–DNA probes more than the others. Interestingly, an important component of the replication protein A complex, RPA2, was found to bind to kiteplatin much more tightly than other proteins. These results may be important for the interpretation of the roles of carrier ligands in platinum(II)-based anticancer complexes.