| Autor: |
Wickham G; Department of Chemistry, University of Wollongong, NSW, Australia., Iannitti P, Boschenok J, Sheil MM |
| Jazyk: |
angličtina |
| Zdroj: |
Rapid communications in mass spectrometry : RCM [Rapid Commun Mass Spectrom] 1995; Vol. Spec No, pp. S197-203. |
| Abstrakt: |
Electrospray ionization mass spectrometry (ESI-MS) has been used to examine the covalent binding of the anti-tumour agents cisplatin and hedamycin with self-complementary oligonucleotides 5'-TACGTA-3', 5'-CACGTG-3', 5'-AGGCCT-3' or 5'-CGTACG-3' as models for binding to cellular DNA. The observation of duplex forms of oligonucleotide adducts of these compounds in the gas phase has been found to correlate with the stability of the adducts in solution. Hedamycin, which both intercalates into and alkylates DNA, enhances the stability of duplex ions in ESI mass spectra. In contrast, the binding of cisplatin is known to destabilise duplexes in solution and only weak double-stranded peaks are observed in the ESI spectra of cisplatin-oligonucleotide adducts. Results of titration experiments with the hedamycin-5'-CACGTG-3' adduct and complementary and non-complementary oligo-nucleotides provide strong evidence that the observed duplex ions are the result of specific base-paired associations in the gas phase, rather than non-specific interactions. Finally, estimates of the extent of cisplatin binding to different sequences based on ESI mass spectra of crude reaction mixtures are found to correlate well with data obtained by reversed-phase high-performance liquid chromatography. This work demonstrates the considerable potential of ESI-MS as a tool for characterization of the interactions of antitumour agents with DNA. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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