Recognition and cleavage of DNA by rebeccamycin- or benzopyridoquinoxaline conjugated of triple helix-forming oligonucleotides.
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.
Arimondo
P B
PB
Laboratoire de Biophysique, UMR 8646 CNRS-Muséum National d'Histoire Naturelle, INSERM U201, Paris, France.
Moreau
P
P
Boutorine
A
A
Bailly
C
C
Prudhomme
M
M
Sun
J S
JS
Garestier
T
T
Hélène
C
C
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001483:Base Sequence; D002227:Carbazoles; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D018983:DNA Footprinting; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D006868:Hydrolysis; D007211:Indoles; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry*; D011810:Quinoxalines / Q000737:chemistry*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D002227:Carbazoles; D007211:Indoles; D009841:Oligonucleotides; D011725:Pyridines; D011810:Quinoxalines; C411084:benzopyridoquinoxaline; D004247:DNA; C053339:rebeccamycin; D004264:DNA Topoisomerases, Type I