Factors Affecting Formation and Structure of DNA Intrastrand Cross-Links by Dinuclear Platinum Complexes

  • Y. Qu
  • M. J. Bloemink
  • K. J. Mellish
  • H. Rauter
  • K. A. Smeds
  • N. Farrell
Part of the NATO ASI Series book series (ASEN2, volume 26)


Dinuclear platinum complexes are currently undergoing pre-clinical evaluation. The development of this series has been driven by the hypothesis that a different spectrum of antitumor activity in comparison to that of cisplatin (cis-[PtCl2(NH3)2], cis-DDP) will be achieved by altering the mode of DNA binding relative to that of cisplatin and its analogues. Dinuclear platinum complexes form a unique array of DNA adducts including (Pt, Pt) interstrand and (Pt, Pt) intrastrand cross-links. A (Pt, Pt) intrastrand adduct between two adjacent guanines is the structural analog of the major adduct formed by cis-DDP2. This cis-DDP-d(GpG) adduct produces a rigid, directed bend 30-35° into the major groove of DNA, confirmed by both X- ray and NMR structural determinations on oligonucleotide fragments containing site-specific adducts3, 4. This bend is recognised by damage recognition proteins containing the HMG-binding domain5. In contrast, the global structural distortions of DNA induced by the dinuclear platinum complexes are recognized only weakly by HMG-domain proteins.6 This contribution summarises our results on the structural reasons for these differences, as exemplified by comparative studies on DNA-DNA intrastrand adducts between adjacent guanines.


Platinum Complex Major Groove Steric Hinderance Dinuclear Platinum Adjacent Guanine 
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Copyright information

© Springer Science+Business Media Dordrecht 1997

Authors and Affiliations

  • Y. Qu
    • 1
  • M. J. Bloemink
    • 1
  • K. J. Mellish
    • 1
  • H. Rauter
    • 1
  • K. A. Smeds
    • 1
  • N. Farrell
    • 1
  1. 1.Department of ChemistryVirginia Commonwealth UniversityRichmondUSA

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