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Interactions of Anticancer Active Platinum(II) Complexes with DNA

Johan Kjellström-2001-01-01-Lund University Publications (Lund University)
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TL;DRAbstract

The kinetics and mechanism for interactions of the anticancer active platinum(II) complexes cis-[PtCl2(NH3)2)], cis-[PtCl2(NH3)(c-C6H11NH2)], and trans-[PtCl2-(NH3)(quinoline)] with DNA have been studied using a combination of HPLC, circular dichroism (CD), UV/vis spectroscopy, and differential scanning calorimetry (DSC). Reactions of the monoaqua forms (charge = +1) of these complexes with single-stranded DNA oligonucleotides, typically between 13-17 bases long, were found to depend on i) the composition of the reaction medium, ii) the exact nature and location of the platination target, and iii) on the DNA structure. The platination reactions were studied in the presence of Na+, Mg2+ and spermidine (spd3+) cations. Increasing concentrations and increasing charge of these electrolytes reduce the rate of platination significantly. The results suggest that the rate dependence on cation concentration occurs as a result of the polyanionic nature of the oligonucleotides, rather than variat

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The kinetics and mechanism for interactions of the anticancer active platinum(II) complexes cis-[PtCl2(NH3)2)], cis-[PtCl2(NH3)(c-C6H11NH2)], and trans-[PtCl2-(NH3)(quinoline)] with DNA have been studied using a combination of HPLC, circular dichroism (CD), UV/vis spectroscopy, and differential scanning calorimetry (DSC). Reactions of the monoaqua forms (charge = +1) of these complexes with single-stranded DNA oligonucleotides, typically between 13-17 bases long, were found to depend on i) the composition of the reaction medium, ii) the exact nature and location of the platination target, and iii) on the DNA structure. The platination reactions were studied in the presence of Na+, Mg2+ and spermidine (spd3+) cations. Increasing concentrations and increasing charge of these electrolytes reduce the rate of platination significantly. The results suggest that the rate dependence on cation concentration occurs as a result of the polyanionic nature of the oligonucleotides, rather than variat

Keywords

ChemistryPlatinumOligonucleotideCircular dichroismPolyelectrolyteCrystallographyNucleotideDNA

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