Low concentrations of acridine dimers inhibit micrococcus AP endonuclease through interaction with apurinic sites in DNA

Chem Biol Interact. 1990;73(2-3):249-60. doi: 10.1016/0009-2797(90)90007-a.

Abstract

The effect of dimeric DNA intercalating compounds was assayed on a purified AP endonuclease from Microccoccus luteus using apurinic supercoiled PM2 DNA as a substrate. Binding on apurinic sites was estimated through the competition with the intercalating compound, 9-NH2-ellipticine, which displays great specificity for apurinic sites. An acridine dimer with a spermine linker is at 0.1 microM the best inhibitor of cleavage at the apurinic site induced either by the AP endonuclease or by 9-NH2-ellipticine. Bisintercalating agents are more effective inhibitors of AP endonuclease than monointercalating ones. Most effective inhibitors among dimers have acridine residues.

MeSH terms

  • Acridines / pharmacology*
  • Apurinic Acid / metabolism*
  • Binding Sites
  • Binding, Competitive
  • DNA, Superhelical / metabolism*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • Deoxyribonuclease IV (Phage T4-Induced)
  • Ellipticines / metabolism
  • Endodeoxyribonucleases / antagonists & inhibitors*
  • Hot Temperature
  • Intercalating Agents
  • Micrococcus / enzymology*
  • Molecular Structure
  • Polynucleotides / metabolism*

Substances

  • Acridines
  • DNA, Superhelical
  • Ellipticines
  • Intercalating Agents
  • Polynucleotides
  • Apurinic Acid
  • 9-aminoellipticine
  • Endodeoxyribonucleases
  • Deoxyribonuclease IV (Phage T4-Induced)
  • DNA-(Apurinic or Apyrimidinic Site) Lyase