Synthesis and DNA conformational changes of non-covalent polynuclear platinum complexes
| Authors | |
|---|---|
| Year of publication | 2004 |
| Type | Article in Periodical |
| Magazine / Source | Journal of Inorganic Biochemistry |
| MU Faculty or unit | |
| Citation | |
| Field | Biophysics |
| Keywords | Non-covalent DNA binding; Polynuclear platinum |
| Description | Polynuclear platinum compounds demonstrate many novel phenomena in their interactions with DNA and proteins as well as novel anti-cancer activities. Previous studies indicated that the high positive charge and the non-coordinated Ącentral linkerĄą of the polynuclear compounds could have major contributions to these features. Therefore, a series of non-covalent polynuclear platinum complexes, [ Pt(NH3)3 2-ŚĚ-Y]n+ (Y = polyamine linker or trans-Pt(NH3)2(H2N(CH2)6NH2)2 ) was synthesized and the DNA interactions of these platinum complexes were investigated. The conformational changes induced by these compounds in polymer DNA were studied by circular dichroism and the reversibility of the transition was tested by subsequent titration with the DNA intercalating agent ethidium bromide (EtBr). Fluorescent quenching was also used to assess the ability of EtBr to intercalate into A and Z-DNA induced by the compounds. The non-covalent polynuclear platinum complexes induced both B Ąú A and B Ąú Z conformational changes in polymer DNA. These conformational changes were partially irreversible. The platinum compound with the spermidine linker, [ Pt(NH3)3 2-ŚĚ-spermidine-N1,N8]Cl5 Ą 2H2O, is more efficient in inducing the conformational changes of DNA and it is less reversible than complexes with other linkers. The melting point study showed that the non-covalent polynuclear platinum complexes stabilized the duplex DNA and the higher the electrical charge of the complexes the greater the stabilization observed. |