ABSTRACT
The ability to introduce DNA damage selectively into a specific cell type eventually to confer cell death is a highly desirable strategy in cancer chemotherapy. One of the most successfully employed agents is the inorganic drug cis-diamminedichloro platinum(II) (cis-DDP), or cisplatin (1). The numerous advances made in understanding the mechanism of action of the drug are summarized in several recent review articles covering a broad range of topics including DNA as the drug target (2), the recognition and processing of cisplatin-DNA adducts (3), proteins recognizing Pt-DNA damage (4,5), cellular consequences of protein binding (6), repair of cisplatindamage (7) and new platinum complexes as potential therapeutics (8). The present chapter focuses on the structural aspects of cisplatin-DNA-protein interactions with an emphasis on recognition of the major adduct, a 1,2-intrastrand cross-link. A wealth of structural information recently made available, including knowledge of a ternary cisplatin-protein-DNA complex and DNA complexes of proteins with the ability to recognize cis-DDP-DNA adducts bound to their natural DNA substrates, reveal striking similarities in the DNA recognition mechanisms.
