Publication details
DNA interactions of bifunctional dinuclear platinum(II) antitumor agents
Authors | |
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Year of publication | 1997 |
Type | Article in Periodical |
Magazine / Source | EUROPEAN JOURNAL OF BIOCHEMISTRY |
MU Faculty or unit | |
Citation | |
Field | Biochemistry |
Keywords | DNA; platinum drug; dinuclear complex; cross-link; anticancer effect |
Description | Modifications of natural DNA in a cell-free medium by dinuclear bisplatinum complexes with equivalent coordination spheres, represented by the general formula [{trans-PtCl(NH3)(2)}(2)(H2N-R-NH2)](2+), where R is a propane or hexane, were studied by various methods of biochemical analysis or molecular biophysics. These methods include binding studies by means of differential-pulse polarography, measurements of melting curves with the aid of absorption spectrophotometry, measurements of CD spectra, ELISA with specific antibodies that recognize DNA modified by platinum complexes, interstrand crosslinking assay employing gel electrophoresis under denaturing conditions and mapping of DNA adducts by means of transcription assays. The results indicated that the major adduct of [{trans-PtCl(NH3)(2)}(2)(H2N-R-NH2)](2+) in DNA was an interstrand cross-link which was formed with a relatively short half-time (approximate to 1 h). At least some types of these interstrand cross-links induced local denaturational changes in the DNA. |