Formation of platinated GG cross-links on DNA by photoactivation of a platinum(IV) azide complex
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- DNA Adducts chemical synthesis isolation & purification MeSH
- Azides chemistry MeSH
- Cisplatin chemistry MeSH
- DNA chemistry MeSH
- Photochemistry MeSH
- Photochemotherapy MeSH
- Transcription, Genetic MeSH
- Guanine chemistry MeSH
- Antineoplastic Agents chemistry MeSH
- Base Sequence MeSH
- Platinum Compounds chemistry MeSH
- Chromatography, High Pressure Liquid MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DNA Adducts MeSH
- Azides MeSH
- Cisplatin MeSH
- DNA MeSH
- Guanine MeSH
- Antineoplastic Agents MeSH
- Platinum Compounds MeSH
Platinum(II) diam(m)ine complexes such as cisplatin are effective anticancer drugs but have accompanying side effects. We are exploring the design of platinum complexes with low toxicity that could be photoactivated selectively at the target site. We show here that the Pt(IV) azide complex cis, trans-[Pt(en)(N(3))(2)(OH)(2)] is unreactive towards DNA until irradiated with visible light. Transcription mapping studies of a 212-bp fragment of pSP73KB plasmid DNA treated with cis, trans-[Pt(en)(N(3))(2)(OH)(2)] and irradiated with visible light showed that the platination sites were similar to those observed for cisplatin, and were mainly in GG sequences. HPLC analysis of enzymatic digests of an irradiated sample of a 40-bp DNA duplex treated with the same complex also revealed preferential formation of GG cross-links. Since such DNA lesions are thought to be responsible for the induction of apoptosis in cancer cells by platinum drugs, the use of unreactive photoactivatable platinum pro-drugs may become an effective strategy for the design of a new generation of platinum anticancer complexes.
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