Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 May 1;88(9):3516–3519. doi: 10.1073/pnas.88.9.3516

Possible catalytic activity of DNA in the reaction between the antitumor drug cis-diamminedichloroplatinum(II) and the intercalator N-methyl-2,7-diazapyrenium.

F Gaucheron 1, J M Malinge 1, A J Blacker 1, J M Lehn 1, M Leng 1
PMCID: PMC51482  PMID: 2023897

Abstract

The platinum(II) complex cis-[Pt(NH3)2(N7-N-methyl-2-diazapyrenium)Cl]2+ formed in the reaction between cis-diamminedichloroplatinum(II) and N-methyl-2,7-diazapyrenium reacts with N7 of guanine residues in DNA. The resulting adduct is kinetically inert within single-stranded DNA. Within double-stranded DNA, it is kinetically inert in 1 M NaClO4 and becomes labile as the salt concentration is decreased. Two products, cis-[Pt(NH3)2(N7-N-methyl-2-diazapyrenium)H2O]3+ and N-methyl-2,7-diazapyrenium, are released. The conformation of the platinated DNA is different in low- and high-salt conditions as shown by the chemical probe diethyl pyrocarbonate. These results are discussed in relation with a possible catalytic role played by the double-stranded DNA.

Full text

PDF
3516

Images in this article

3517Image
on p.3517
3517Image
on p.3517
3518Image
on p.3518

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Comess K. M., Costello C. E., Lippard S. J. Identification and characterization of a novel linkage isomerization in the reaction of trans-diamminedichloroplatinum(II) with 5'-d(TCTACGCGTTCT). Biochemistry. 1990 Feb 27;29(8):2102–2110. doi: 10.1021/bi00460a020. [DOI] [PubMed] [Google Scholar]
  2. Eastman A. Reevaluation of interaction of cis-dichloro(ethylenediamine)platinum(II) with DNA. Biochemistry. 1986 Jul 1;25(13):3912–3915. doi: 10.1021/bi00361a026. [DOI] [PubMed] [Google Scholar]
  3. Eastman A. The formation, isolation and characterization of DNA adducts produced by anticancer platinum complexes. Pharmacol Ther. 1987;34(2):155–166. doi: 10.1016/0163-7258(87)90009-x. [DOI] [PubMed] [Google Scholar]
  4. Herr W. Diethyl pyrocarbonate: a chemical probe for secondary structure in negatively supercoiled DNA. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8009–8013. doi: 10.1073/pnas.82.23.8009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hollis L. S., Amundsen A. R., Stern E. W. Chemical and biological properties of a new series of cis-diammineplatinum(II) antitumor agents containing three nitrogen donors: cis-[Pt(NH3)2(N-donor)Cl]+. J Med Chem. 1989 Jan;32(1):128–136. doi: 10.1021/jm00121a024. [DOI] [PubMed] [Google Scholar]
  6. Johnston B. H., Rich A. Chemical probes of DNA conformation: detection of Z-DNA at nucleotide resolution. Cell. 1985 Oct;42(3):713–724. doi: 10.1016/0092-8674(85)90268-5. [DOI] [PubMed] [Google Scholar]
  7. Lippard S. J., Hoeschele J. D. Binding of cis- and trans-dichlorodiammineplatinum(II) to the nucleosome core. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6091–6095. doi: 10.1073/pnas.76.12.6091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Malinge J. M., Leng M. Reaction of nucleic acids and cis-diamminedichloroplatinum(II) in the presence of intercalating agents. Proc Natl Acad Sci U S A. 1986 Sep;83(17):6317–6321. doi: 10.1073/pnas.83.17.6317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Malinge J. M., Leng M. Reactivity of monofunctional cis-platinum adducts as a function of DNA sequence. Nucleic Acids Res. 1988 Aug 11;16(15):7663–7672. [PMC free article] [PubMed] [Google Scholar]
  10. Malinge J. M., Sip M., Blacker A. J., Lehn J. M., Leng M. Formation of a DNA monofunctional cis-platinum adduct cross-linking the intercalating drug N-methyl-2,7-diazapyrenium. Nucleic Acids Res. 1990 Jul 11;18(13):3887–3891. doi: 10.1093/nar/18.13.3887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Rice J. A., Crothers D. M., Pinto A. L., Lippard S. J. The major adduct of the antitumor drug cis-diamminedichloroplatinum(II) with DNA bends the duplex by approximately equal to 40 degrees toward the major groove. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4158–4161. doi: 10.1073/pnas.85.12.4158. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Schwartz A., Marrot L., Leng M. Conformation of DNA modified at a d(GG) or a d(AG) site by the antitumor drug cis-diamminedichloroplatinum(II). Biochemistry. 1989 Oct 3;28(20):7975–7979. doi: 10.1021/bi00446a001. [DOI] [PubMed] [Google Scholar]
  13. Vogt N., Marrot L., Rousseau N., Malfoy B., Leng M. Chloroacetaldehyde reacts with Z-DNA. J Mol Biol. 1988 Jun 20;201(4):773–776. doi: 10.1016/0022-2836(88)90474-3. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES