Modelling steric effects in DNA-binding platinum(II)-am(m)ine complexes

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Abstract

A repulsive energy strategy has been employed in an attempt to delineate the steric contribution to the biological profile of a variety of platinum-am(m)ine complexes. Thus, relative steric descriptors have been calculated for the amine ligands themselves by the Ligand Repulsive Energy (LRE) methodology. This has been extended to a Complex Repulsive Energy (CRE) strategy whereby the steric requirements of the approach of a metal complex to a site on a target molecule may be evaluated. Specifically, the monodentate approach of a variety of platinum-am(m)ine complexes to the N7 site of a guanine moiety has been considered. The steric descriptors thus obtained have been used in QSAR analysis, resulting in improved regression equations. Attempts have also been made to relate the above descriptors to various biological indicators for given series of complexes. These investigations suggest an optimum steric requirement for minimum toxicity, which could aid in the rational design of such agents.

Original languageEnglish
Pages (from-to)589-606
Number of pages18
JournalJournal of Computer-Aided Molecular Design
Volume10
Issue number6
Publication statusPublished - 1 Dec 1996
Externally publishedYes

Keywords

  • Biological indicators
  • Electronic effects
  • QSAR
  • Repulsive energy
  • Transport effects

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