Possible catalytic activity of DNA in the reaction between the antitumor drug cis-diamminedichloroplatinum(II) and the intercalator N-methyl-2,7-diazapyrenium.
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.
Gaucheron
F
F
Centre de Biophysique Moléculaire, Orléans, France.
Malinge
J M
JM
Blacker
A J
AJ
Lehn
J M
JM
Leng
M
M
D001483:Base Sequence; D002945:Cisplatin / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004277:DNA, Single-Stranded / Q000737:chemistry; D066298:In Vitro Techniques; D007364:Intercalating Agents / Q000737:chemistry*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009994:Osmolar Concentration; D010618:Phenanthrolines / Q000737:chemistry*
D004277:DNA, Single-Stranded; D007364:Intercalating Agents; D009838:Oligodeoxyribonucleotides; D010618:Phenanthrolines; C065034:N-methyl-2,7-diazapyrenium; D004247:DNA; D002945:Cisplatin