DNA-binding affinities and sequence selectivity of quaternary benzophenanthridine alkaloids sanguinarine, chelerythrine, and nitidine

Bioorg Med Chem. 2006 Aug 15;14(16):5439-45. doi: 10.1016/j.bmc.2006.05.012. Epub 2006 May 30.

Abstract

A comparative study on the intercalating binding of sanguinarine, chelerythrine, and nitidine with CT DNA, poly(dG-dC).poly(dG-dC), poly(dA-dT).poly(dA-dT), and seven sequence-designed double-stranded oligodeoxynucleotides has been performed using fluorometric and spectrophotometric techniques, aiming at providing insights into their sequence selectivity for DNA-binding. The results show that both sanguinarine and nitidine bind preferentially to DNA containing alternating GC base pairs [d(TGCGCA)(2)], while chelerythrine exhibits quite distinct sequence selectivity from sanguinarine, which shows a high specificity for DNA containing contiguous GC base pairs [5'-TGGGGA-3'/3'-ACCCCT-5'].

Publication types

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

MeSH terms

  • Alkaloids / chemistry
  • Alkaloids / pharmacology*
  • Base Pairing
  • Base Sequence
  • Benzophenanthridines
  • Binding Sites
  • DNA / chemistry
  • DNA / drug effects*
  • DNA / metabolism
  • Intercalating Agents / chemistry
  • Intercalating Agents / metabolism
  • Isoquinolines
  • Phenanthridines / chemistry
  • Phenanthridines / pharmacology*
  • Polydeoxyribonucleotides / chemistry
  • Polydeoxyribonucleotides / metabolism
  • Spectrometry, Fluorescence
  • Spectrophotometry

Substances

  • Alkaloids
  • Benzophenanthridines
  • Intercalating Agents
  • Isoquinolines
  • Phenanthridines
  • Polydeoxyribonucleotides
  • DNA
  • calf thymus DNA
  • nitidine
  • sanguinarine
  • chelerythrine