Effects of quinoline as ligand in binding of mononuclear and dinuclear platinum complexes to DNA
1997; Elsevier BV; Volume: 255; Issue: 1 Linguagem: Inglês
10.1016/s0020-1693(96)05196-1
ISSN1873-3255
AutoresMalkhaz Kharatishvili, Michael T. Mathieson, Nicholas P. Farrell,
Tópico(s)DNA and Nucleic Acid Chemistry
ResumoThe DNA binding and interstrand cross-linking properties of trans- and cis-[PtCl2 (NH3)(quinoline)] (I and II, respectively) and a quinoline-substituted dinuclear platinum compound [{trans-PtCl(NH3)(quin)}2H2N(CH2)6NH2](NO3)2 (III) are reported. The dinuclear compound was examined also for its ability to cause conformational changes in poly[(dG–dC)]·poly[(dG–dC)]. For DNA binding studies a UV spectrophotometric method of rb determination has been used, allowing measurement of the concentration of a platinum complex bound to DNA using UV absorbance of a ligand, in this case, quinoline. Comparison was made with atomic absorption (AAS) measurements of Pt determination which showed valid agreement between the two methods. In the case of mononuclear complexes, geometry plays an important role in binding as proved by increased binding of the trans- over the cis-isomer. For the dinuclear complex, binding saturates at concentrations of approximately 150–200 μM reaching the level of relative binding of rb∼0.25. Interstrand cross-linking of the dinuclear compound was compared with [{trans-PtCl(NH3)2}2H2N(CH2)6NH2](NO3)2 (IV). Both dinuclear compounds showed similar and very strong interstrand cross-linking efficiency. Binding of III to poly[(dG–dC)]·poly[(dG–dC)] changes intensities and shapes of both positive and negative bands of the polymer CD spectrum, although the overall behavior of these changes indicates that the polynucleotide remains in the B conformation.
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