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

Frédéric Gaucheron (1) , Jean-Marc Malinge (1) , A. John Blacker (2) , Jean-Marie Lehn (2) , Marc Leng (1)

1 CBM - Centre de biophysique moléculaire
2 UNIV Louis Pasteur - Institut Le Bel [Strasbourg]

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.

Domaines: Sciences du Vivant [q-bio]

Frédéric Gaucheron, Jean-Marc Malinge, A. John Blacker, Jean-Marie Lehn, Marc Leng. Possible catalytic activity of DNA in the reaction between the antitumor drug cis-diamminedichloroplatinum(II) and the intercalator N-methyl-2,7-diazapyrenium.. Proceedings of the National Academy of Sciences of the United States of America, 1991, 88 (9), pp.3516-3519. ⟨10.1073/pnas.88.9.3516⟩. ⟨hal-02134694⟩