DNA crosslinking via platinum coordination complex formation

DNA crosslinking via platinum coordination complex formation refers to the process by which platinum-based compounds, such as cisplatin and related analogs, form covalent bonds with DNA. These interactions result in the creation of intra- and interstrand crosslinks within the DNA double helix, as well as ternary complexes involving both DNA and proteins. This mechanism is central to the cytotoxic effects of many antitumor drugs. These crosslinks distort the helical structure of DNA, inhibiting essential processes such as replication and transcription. Ternary complexes involving both protein and platinated DNA are particularly bulky lesions that are more persistent than simple adducts; they inhibit repair mechanisms like nucleotide excision repair more effectively than standard intrastrand or monofunctional adducts. The inability to properly replicate or transcribe damaged DNA leads ultimately to cell cycle arrest and apoptosis—effects exploited in cancer chemotherapy.

Covalent binding at N7 positions on purines; forms intra/interstrand/protein-DNA crosslinks