Ligand-induced formation of triple helices with antiparallel third strands containing G and T.
We have examined the effects of benzopyridoindole derivatives on triple helices with antiparallel third strands. Absorption spectroscopy, footprinting, and gel retardation experiments demonstrate that a benzopyridoindole derivative (BePI) is able to induce formation of a triple helix with an antiparallel (G, T)-containing third strand, which does not form in the absence of this ligand. This triple-helical complex is very stable with a half-dissociation temperature as high as 51 degrees C, and its formation is pH independent. Antiparallel oligonucleotides containing thymine and guanine bind strongly to double-helical DNA under physiological conditions in the presence of only 0.5 microM BePI. Formation of a BePI-stabilized triple helix strongly inhibits cleavage of the target duplex by DNase I.
Escudé
C
C
Laboratoire de Biophysique, INSERM U 201, CNRS URA 481, Paris, France.
Sun
J S
JS
Nguyen
C H
CH
Bisagni
E
E
Garestier
T
T
Hélène
C
C
D001483:Base Sequence; D004247:DNA / Q000138:chemical synthesis* / Q000737:chemistry* / Q000302:isolation & purification; D018983:DNA Footprinting; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D007211:Indoles; D008024:Ligands; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011725:Pyridines; D013056:Spectrophotometry, Ultraviolet
D007202:Indicators and Reagents; D007211:Indoles; D008024:Ligands; D011725:Pyridines; C082732:3-methoxy-7H-8-methyl-11-((3'-amino)propylamino)benzo(e)pyrido(4,3-b)indole; D004247:DNA