Influence of carbonate on the binding of carboplatin to DNA

Robert S. Sorokanich, Anthony J. Di Pasqua, Martina Geier, James C. Dabrowiak

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The reaction of aged carboplatin (reaction of carboplatin in 24 mM NaHCO3 for 45 h, 37°, pH 8.6) with pBR322 DNA at 0<r<2.8, where r=[drug]/[DNA-bp], in 24 mM HEPES buffer, pH 7.4, for 24 h, followed by agarose gel electrophoresis showed DNA mobility changes consistent with unwinding closed circular DNA. However, identical experiments conducted in a two-buffer system, 24 mM HEPES plus 24 mM carbonate, showed no DNA mobility changes, indicating that carbonate blocks formation of the 1,2 intrastrand cross-link on DNA. Studies with aged carboplatin and with cisplatin carried out with ca. 4.0<r<10.0 in the two-buffer system show that some DNA binding and unwinding occurs for both drugs. Since carbonate inhibits the binding of aged carboplatin and cisplatin to DNA, carbonate present in the body likely modulates the reactivity of these drugs with a variety of biological targets including DNA.

Original languageEnglish (US)
Pages (from-to)1540-1544
Number of pages5
JournalChemistry and Biodiversity
Volume5
Issue number8
DOIs
StatePublished - Dec 1 2008

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Chemistry(all)
  • Molecular Medicine
  • Molecular Biology

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    Sorokanich, R. S., Di Pasqua, A. J., Geier, M., & Dabrowiak, J. C. (2008). Influence of carbonate on the binding of carboplatin to DNA. Chemistry and Biodiversity, 5(8), 1540-1544. https://doi.org/10.1002/cbdv.200890142