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

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

doi:10.1021/tx100170p

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 journal › Article › peer-review

9 Scopus citations

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 language	English (US)
Pages (from-to)	1148-1150
Number of pages	3
Journal	Chemical research in toxicology
Volume	23
Issue number	7
DOIs	https://doi.org/10.1021/tx100170p
State	Published - Jul 19 2010
Externally published	Yes

ASJC Scopus subject areas

Toxicology

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/tx100170p

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title = "Probing platinum-adenine-N3 adduct formation with DNA minor-groove Binding agents",

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.",

author = "Lu Rao and West, {Tiffany K.} and Gilda Saluta and Kucera, {Gregory L.} and Ulrich Bierbach",

year = "2010",

month = jul,

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doi = "10.1021/tx100170p",

language = "English (US)",

volume = "23",

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journal = "Chemical research in toxicology",

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T1 - Probing platinum-adenine-N3 adduct formation with DNA minor-groove Binding agents

AU - Rao, Lu

AU - West, Tiffany K.

AU - Saluta, Gilda

AU - Kucera, Gregory L.

AU - Bierbach, Ulrich

PY - 2010/7/19

Y1 - 2010/7/19

N2 - 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.

AB - 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.

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JO - Chemical research in toxicology

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IS - 7

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

Abstract

ASJC Scopus subject areas

UN SDGs

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