Intrinsic conformational preferences of the Hoechst dye family and their influence of DNA binding

Eur J Biochem. 1996 Jul 15;239(2):376-83. doi: 10.1111/j.1432-1033.1996.0376u.x.

Abstract

Quantum mechanical calculations have been used to investigate the molecular conformation of the Hoechst family of DNA-binding dyestuffs. Compounds in which the phenolic substituent adopts either a meta or para position were studied. Two different environments have been considered, which are the gas phase and aqueous solution; the conformation in aqueous solution has been modeled through a self-consistent reaction field strategy. The results clearly indicate that Hoechst dyes do not adopt a planar conformation and that the degree of planarity is controlled by the external environment. A comparison with experimental data reveals that the conformation of Hoechst dyes in the gas phase is similar to that observed in DNA complexes by X-ray crystallography. In aqueous solution, the conformation deviates from planarity more than in the gas phase, since non-bonded interactions with the solvent offset the loss of conjugative interactions. The role of the drug conformation in the binding mechanism with DNA is discussed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Benzimidazoles* / chemistry
  • Bisbenzimidazole* / chemistry
  • Coloring Agents* / chemistry
  • DNA*
  • Electrochemistry
  • Fourier Analysis
  • Models, Molecular
  • Molecular Conformation
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides / chemistry*
  • Solutions
  • Stereoisomerism
  • Structure-Activity Relationship
  • Thermodynamics

Substances

  • Benzimidazoles
  • Coloring Agents
  • Oligodeoxyribonucleotides
  • Solutions
  • DNA
  • Bisbenzimidazole