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 journalArticle

8 Citations (Scopus)

Abstract

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
Volume23
Issue number7
DOIs
StatePublished - Jul 19 2010
Externally publishedYes

Fingerprint

Adenine
Platinum
DNA
Netropsin
ethylenediamine
DNA Cleavage
Alkylating Agents
Cytotoxins
Cell proliferation
Guanine
Cytotoxicity
Bioactivity
Binders
1-(2-(acridin-9-ylamino)ethyl)-1,3-dimethylthiourea
Assays
Cells
Cell Proliferation
Neoplasms

ASJC Scopus subject areas

  • Toxicology

Cite this

Probing platinum-adenine-N3 adduct formation with DNA minor-groove Binding agents. / Rao, Lu; West, Tiffany K.; Saluta, Gilda; Kucera, Gregory L.; Bierbach, Ulrich.

In: Chemical Research in Toxicology, Vol. 23, No. 7, 19.07.2010, p. 1148-1150.

Research output: Contribution to journalArticle

Rao, Lu ; West, Tiffany K. ; Saluta, Gilda ; Kucera, Gregory L. ; Bierbach, Ulrich. / Probing platinum-adenine-N3 adduct formation with DNA minor-groove Binding agents. In: Chemical Research in Toxicology. 2010 ; Vol. 23, No. 7. pp. 1148-1150.
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