Interaction of Platinum Antitumor Compounds with DNA

  • C. A. Lepre
  • S. J. Lippard
Part of the Nucleic Acids and Molecular Biology book series (NUCLEIC, volume 4)


The cis and trans isomers of diamminedichloroplatinum(II) (cis- and trans- DDP, Fig. 1) have enjoyed a long history in inorganic chemistry, having first been synthesized and separated in the 19th century. Until recently, however, complexes of the platinum group metals were of little interest to medicinal chemists owing to their reputation as highly toxic compounds. Interest in the biological effects of platinum complexes was greatly stimulated following reports that cis,-[Pt(NH3)2CI4] and related cis-coordinated platinum ammine chloride complexes induced filamentous growth in Escherichia coli, an indication of DNA damage (Rosenberg et al. 1965; Rosenberg et al. 1967; Rosenberg 1980). Subsequent demonstration that cis-DDP exhibited antitumor activity in mice led to clinical trials and eventual FDA approval for its use as an anticancer drug (Rosenberg et al. 1969; Rosenberg 1980).





base pair




circular dichroism




drug to nucleotide ratio


enthalpy of activation


entropy of activation










deoxyribonucleic acid






2’deoxy guanosine-5’-monophosphate


nuclear magnetic resonance


parts per million


ribonucleic acid






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Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • C. A. Lepre
  • S. J. Lippard
    • 1
  1. 1.Department of ChemistryMassachussets Institute of TechnologyCambridgeUSA

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