Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1991 Apr 11;19(7):1483–1489. doi: 10.1093/nar/19.7.1483

The reaction of platinum(II) complexes with DNA. Kinetics of intrastrand crosslink formation in vitro.

F Bernges 1, E Holler 1
PMCID: PMC333905  PMID: 2027756

Abstract

The kinetics of the formation of bifunctional DNA platinum(II) adducts (DNA-crosslinks) have been investigated by endonuclease digestion and subsequent HPLC analysis of the soluble nucleotides and nucleotide platinum(II) adducts. The results indicate two waves of crosslinking [rate constants (0.2-0.3) min-1 and (0.015-0.025) min-1] that correlate with changes in ultra violet absorbance and ethidium bromide dependent fluorescence intensity, previously interpreted in terms of two consecutive, local conformational rearrangements of platinum-DNA (Schaller, W., Reisner, H., and Holler, E. (1987) Biochemistry 26, 943-950). The formation of crosslinks at sequences d(GpG) and d(GpNpG) follows identical kinetics. A minimal reaction mechanism is proposed for the binding of cis-diamminedichloroplatinum(II) to DNA under in vitro conditions. The approximately 3-fold higher rate for meso-[1,2-bis(2,6-dichloro-4- hydroxyphenyl)ethylenediamine]diaquaplatinum(II) in comparison to the rate for cis-diamminediaquaplatinum(II) indicates that crosslink formation is affected by the nature of the non-leaving platinum ligand(s).

Full text

PDF
1483

Selected References

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

  1. Bernges F., Dörner G., Holler E. Escherichia coli DNA polymerase I: inherent exonuclease activities differentiate between monofunctional and bifunctional adducts of DNA and cis- or trans-diamminedichloroplatinum(II). An exonuclease investigation of the kinetics of the adduct formation. Eur J Biochem. 1990 Aug 17;191(3):743–753. doi: 10.1111/j.1432-1033.1990.tb19183.x. [DOI] [PubMed] [Google Scholar]
  2. Eastman A. Characterization of the adducts produced in DNA by cis-diamminedichloroplatinum(II) and cis-dichloro(ethylenediamine)platinum(II). Biochemistry. 1983 Aug 2;22(16):3927–3933. doi: 10.1021/bi00285a031. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Eastman A. Separation and characterization of products resulting from the reaction of cis-diamminedichloroplatinum (II) with deoxyribonucleosides. Biochemistry. 1982 Dec 21;21(26):6732–6736. doi: 10.1021/bi00269a018. [DOI] [PubMed] [Google Scholar]
  5. Fichtinger-Schepman A. M., van der Veer J. L., den Hartog J. H., Lohman P. H., Reedijk J. Adducts of the antitumor drug cis-diamminedichloroplatinum(II) with DNA: formation, identification, and quantitation. Biochemistry. 1985 Jan 29;24(3):707–713. doi: 10.1021/bi00324a025. [DOI] [PubMed] [Google Scholar]
  6. Johnson N. P., Hoeschele J. D., Rahn R. O. Kinetic analysis of the in vitro binding of radioactive cis- and trans-dichlorodiammineplatinum(II) to DNA. Chem Biol Interact. 1980 May;30(2):151–169. doi: 10.1016/0009-2797(80)90122-2. [DOI] [PubMed] [Google Scholar]
  7. Kozelka J., Archer S., Petsko G. A., Lippard S. J., Quigley G. J. Molecular mechanics modeling of oligonucleotide adducts of the antitumor drug cis-diamminedichloroplatinum(II). Biopolymers. 1987 Aug;26(8):1245–1271. doi: 10.1002/bip.360260804. [DOI] [PubMed] [Google Scholar]
  8. Kozelka J., Chottard J. C. How does cisplatin alter DNA structure? A molecular mechanics study on double-stranded oligonucleotides. Biophys Chem. 1990 Apr;35(2-3):165–178. doi: 10.1016/0301-4622(90)80006-s. [DOI] [PubMed] [Google Scholar]
  9. Lepre C. A., Chassot L., Costello C. E., Lippard S. J. Synthesis and characterization of trans-[Pt(NH3)2Cl2] adducts of d(CCTCGAGTCTCC).d(GGAGACTCGAGG). Biochemistry. 1990 Jan 23;29(3):811–823. doi: 10.1021/bi00455a031. [DOI] [PubMed] [Google Scholar]
  10. Loehrer P. J., Einhorn L. H. Drugs five years later. Cisplatin. Ann Intern Med. 1984 May;100(5):704–713. doi: 10.7326/0003-4819-100-5-704. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Marrot L., Leng M. Chemical probes of the conformation of DNA modified by cis-diamminedichloroplatinum(II). Biochemistry. 1989 Feb 21;28(4):1454–1461. doi: 10.1021/bi00430a005. [DOI] [PubMed] [Google Scholar]
  13. Miller K. J., Taylor E. R., Basch H., Krauss M., Stevens W. J. A theoretical model for the binding of cis-Pt(NH3)2(+2) to DNA. J Biomol Struct Dyn. 1985 Jun;2(6):1157–1171. doi: 10.1080/07391102.1985.10507630. [DOI] [PubMed] [Google Scholar]
  14. Mong S., Daskal Y., Prestayko A. W., Crooke S. T. DNA supercoiling, shortening, and induction of single-strand regions by cis-diamminedichloroplatinum(II). Cancer Res. 1981 Oct;41(10):4020–4026. [PubMed] [Google Scholar]
  15. Pinto A. L., Lippard S. J. Binding of the antitumor drug cis-diamminedichloroplatinum(II) (cisplatin) to DNA. Biochim Biophys Acta. 1985;780(3):167–180. doi: 10.1016/0304-419x(85)90001-0. [DOI] [PubMed] [Google Scholar]
  16. Pinto A. L., Lippard S. J. Sequence-dependent termination of in vitro DNA synthesis by cis- and trans-diamminedichloroplatinum (II). Proc Natl Acad Sci U S A. 1985 Jul;82(14):4616–4619. doi: 10.1073/pnas.82.14.4616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Roberts J. J., Thomson A. J. The mechanism of action of antitumor platinum compounds. Prog Nucleic Acid Res Mol Biol. 1979;22:71–133. doi: 10.1016/s0079-6603(08)60799-0. [DOI] [PubMed] [Google Scholar]
  18. Rosenberg B., VanCamp L., Trosko J. E., Mansour V. H. Platinum compounds: a new class of potent antitumour agents. Nature. 1969 Apr 26;222(5191):385–386. doi: 10.1038/222385a0. [DOI] [PubMed] [Google Scholar]
  19. Schaller W., Reisner H., Holler E. Kinetic investigation of the DNA platination reaction: evidence for a transient adduct between deoxyribonucleic acid and cis-platinum(II). Biochemistry. 1987 Feb 10;26(3):943–950. doi: 10.1021/bi00377a039. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Scovell W. M., Capponi V. J. Cis-diamminedichloroplatinum(II) modified DNA stimulates far greater levels of S1 nuclease sensitive regions than does the modification produced by the trans- isomer. Biochem Biophys Res Commun. 1982 Aug;107(3):1138–1143. doi: 10.1016/0006-291x(82)90640-4. [DOI] [PubMed] [Google Scholar]
  22. Scovell W. M., O'Connor T. Interaction of aquated cis-[NH3)2Ptii]with nucleic acid constituents. 1. Ribonucleosides. J Am Chem Soc. 1977 Jan 5;99(1):120–126. doi: 10.1021/ja00443a023. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES