Table of Contents
Metal-Based Drugs
Volume 5 (1998), Issue 4, Pages 197-206

Steric Determinants of Pt/DNA Interactions and Anticancer Activity

1School of Chemistry, University of Sydney, NSW 2006, Australia
2School of Science, Griffith University, Nathan 4111, QLD, Australia

Received 30 June 1998; Accepted 14 July 1998

Copyright © 1998 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Studies directed at establishing the structural features that control Pt/DNA interactions and the anticancer activity of Pt drugs are described. [H1,N15]-HSQC 2D NMR spectroscopic studies of the reactions of cisplatin with oligonucleotides containing ApG and GpA binding sites reveal dramatic differences in the rates of formation of monofunctional adducts at the two sites. When the reactant is cis-[Pt(NH3)2(OH2)2]2+ no such differences are observed suggesting that outer-sphere interactions between the reactant and the oligonucleotide may play a substantial role in determining the rates. Rates of closure to the bifunctional adducts are similar to those observed for cisplatin. Studies of the adduct profiles formed by sterically bulky and/or optically active complexes reveal that steric interactions play a major role in mediating the binding of Pt(ll) to DNA but that hydrogen bonds play less of a role. In vitro cytotoxic activities for these complexes do not always follow the trends that would be expected on the basis of the adduct profiles.