The Influence of the 3’-Base on the Kinetics of the Binding of [PtCl(dien)]Cl to the Dinucleotides d(GpH) (H = A,C,T)

  • E. L. M. Lempers
  • K. Inagaki
  • J. Reedijk
Part of the Developments in Oncology book series (DION, volume 54)

Abstract

It is generally accepted that platinum-DNA interactions are responsible for the antitumor activity of bifunctional Pt-compounds of the type cis-PtX2(amine)2 (1,2). The reaction of these Pt-compounds with DNA occurs in a two-step mechanism. The first binding step consists exclusively of binding to guanine at the N7 position. The second binding step depends on the kind of neighbouring base of the coordinated guanine. When this base is another guanine a GG-chelate will be formed. Therefore on statistical grounds one would expect 37% of the GG-chelate to be formed. However, in practice a much higher yield of the GG-chelate (65%) was found (3). Apparently, the formation of the GG-chelate cannot be explained by using statistics only. It seems that there is some kind of directing effect of Pt-compounds to GG-sequences in the DNA. This raises the question, whether there is also an influence of the other three bases (cytosine, adenine and thymine) attached to a guanine on the binding of platinum to that particular guanine. Therefore competition experiments between the several d(HpG) compounds and between the several d(GpH) compounds were set up. By using the mono-functional [PtCl(dien)]Cl the first binding step can be represented.

Keywords

Sugar Platinum Adenine Dien Nucleoside 

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References

  1. 1.
    Reedijk, J. Pure & Appl. Chem. 59, 181 (1987).CrossRefGoogle Scholar
  2. 2.
    Lippard, S.J. Pure & Appl. Chem. 59, 731 (1987).CrossRefGoogle Scholar
  3. 3.
    Fichtinger-Schepman, A.M.J., Van der Veer, J.L., den Hartog, J.H.J., Lohman, P.H.M., Reedijk, J. Biochemistry 24, 707 (1985).PubMedCrossRefGoogle Scholar
  4. 4.
    Van der Veer, J.L., Noteborn, H.P.J.M., Van der Elst, H., Reedijk, J. Inorg. Chim. Acta. 131, 000 (1987).Google Scholar
  5. 5.
    Van der Marel, G.A., Van Boeckel, C.A.A., Wille, G., Van Boom, J.H. Tetrahedron Lett. 3887 (1981).Google Scholar
  6. 6.
    Watt, G.W., Cude, W.A. Inorg. Chem. 7, 335 (1968).CrossRefGoogle Scholar
  7. 7.
    Marcelis, A.T.M., Reedijk, J. Recl. Trav. Chim. Pays-Bas 102, 121 (1983).CrossRefGoogle Scholar
  8. 8.
    Marcelis, A.T.M., Erkelens, C, Reedijk, J. Inorg. Chim. Acta. Acta. 91, 129 (1984).CrossRefGoogle Scholar

Copyright information

© Martinus Nijhoff Publishing, Boston 1988

Authors and Affiliations

  • E. L. M. Lempers
  • K. Inagaki
  • J. Reedijk

There are no affiliations available

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