Probing platinum-adenine-N3 adduct formation with DNA minor-groove Binding agents

Lu Rao, Tiffany K. West, Gilda Saluta, Gregory L. Kucera, Ulrich Bierbach

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Me-lex py/py, an adenine-N3-selective alkylating agent, and the reversible minor-groove binder netropsin were used to probe the formation of unusual minor-groove adducts by the cytotoxic hybrid agent PT-ACRAMTU ([PtCl(en)(ACRAMTU)](NO 3) 2; en = ethane-1,2-diamine, ACRAMTU = 1-[2-(acridin-9-ylamino)ethyl]-1,3-dimethylthiourea). PT-ACRAMTU was found by chemical footprinting to inhibit specific Me-lex-mediated DNA cleavage at several adenine sites but not at nonspecific guanine, which is consistent with the platination of adenine-N3. In a cell proliferation assay, a significant decrease in cytotoxicity was observed for PT-ACRAMTU, when cancer cells were pretreated with netropsin, suggesting that minor-groove adducts in cellular DNA contribute to the biological activity of the hybrid agent.

Original languageEnglish (US)
Pages (from-to)1148-1150
Number of pages3
JournalChemical research in toxicology
Issue number7
StatePublished - Jul 19 2010
Externally publishedYes

ASJC Scopus subject areas

  • Toxicology


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