Publication details

Synthesis and DNA conformational changes of non-covalent polynuclear platinum complexes

Authors

QU Yun HARRIS Amanda PETZ Andrea KABOLIZADEH Peyman PENAZOVA Hana FARRELL Nicholas

Year of publication 2004
Type Article in Periodical
Magazine / Source Journal of Inorganic Biochemistry
MU Faculty or unit

Faculty of Education

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.

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