Recognition and cleavage of DNA by rebeccamycin- or benzopyridoquinoxaline conjugated of triple helix-forming oligonucleotides

Bioorg Med Chem. 2000 Apr;8(4):777-84. doi: 10.1016/s0968-0896(00)00012-2.

Abstract

Indolocarbazole and benzopyridoquinoxaline derivatives have been shown to have anti-tumor activity and to stimulate DNA topoisomerase I-mediated cleavage. Two indolocarbazole compounds (R-6 and R-95) and one benzopyridoquinoxaline derivative (BPQ(1256)) were covalently attached to the 3'-end of a 16mer triple helix-forming oligonucleotide (TFO). These conjugates bind to DNA with a higher affinity than the unsubstituted oligonucleotides. Furthermore, they induce topoisomerase I-mediated and triplex-directed DNA cleavage in a sequence-specific manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoglycosides*
  • Anti-Bacterial Agents / chemistry*
  • Base Sequence
  • Carbazoles*
  • DNA / chemistry
  • DNA / drug effects*
  • DNA / metabolism
  • DNA Footprinting
  • DNA Topoisomerases, Type I / metabolism
  • Hydrolysis
  • Indoles*
  • Nucleic Acid Conformation*
  • Oligonucleotides / chemistry
  • Oligonucleotides / pharmacology*
  • Pyridines / chemistry*
  • Quinoxalines / chemistry*

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Carbazoles
  • Indoles
  • Oligonucleotides
  • Pyridines
  • Quinoxalines
  • benzopyridoquinoxaline
  • DNA
  • rebeccamycin
  • DNA Topoisomerases, Type I