Binding of the transition metal ion [(H20)(NH3)5Ru(II)]2+ to nucleosomal core and internucleosomal DNA |
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Authors: | Kenneth A Marx Ray Kruger Michael J Clarke |
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Institution: | (1) Biochemistry Ph.D. Program, Department of Chemistry, University of Lowell, One University Ave., 01854 Lowell, MA, USA;(2) Department of Chemistry, Boston College, 02167 Chestnut Hill, MA, USA |
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Abstract: | The goal of this study is to establish the nature of pentammineruthenium(III) binding to DNA in intact mouse liver nuclei. Also, we wish to determine whether the nucleosomal organization of mouse chromatin has a substantial effect on the relative Ru(III) binding levels of internucleosomal and nucleosomal core DNA. These questions are important because ammineruthenium compounds share chemical and biological properties with the cis-dichlorodiammineplatinum(II) or cisplatin chemotherapeutic agent. Therefore, they represent a potential class of new chemotherapeutic agents. We find that in intact nuclei the predominant DNA binding site for pentammineruthenium(II), followed by air oxidation to pentammineruthenium(III), is N-7 guanine, as is the case with cisplatin. Also, the Ru(III) distribution between internucleosomal and nucleosomal core DNA was found to be nearly identical as probed with three non-specific deoxyribonucleases. |
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Keywords: | aquopentammineruthenium(II) reaction oxidation to pentaamineruthenium(III) N-7 guanine ligand chromatin DNA binding nucleosomal vs internucleosomal DNA |
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