Probing intercalation and conformational effects of the anticancer drug 2-methyl-9-hydroxyellipticinium acetate in DNA fragments with circular dichroism.
Circular dichroism was applied to the analysis of drug-DNA associations. With the octanucleotide d(TGACGTCA) (octanucleotide I), which is the cAMP-responsive element (CRE) in gene promoters and its reverse d(ACTGCAGT) (octanucleotide II), it was demonstrated that the anticancer polyaromatic agent celiptium intercalates into DNA base pairs with its long direction perpendicular to both the DNA-helix axis and the base-pair long axis and induces larger conformational changes in the CpG-containing octanucleotide I CRE than in its reverse-sequence octanucleotide II. It was concluded that CD is a powerful and sensitive technique to discriminate between drug-binding modes of DNA, to define the geometry of the chromophore inserted into base pairs and, finally, to measure sequence-dependent conformational changes induced by intercalation in DNA. We anticipate that these studies will contribute to a better understanding of the molecular bases that underlie the mechanism of action of those cytotoxic drugs which interfere with the DNA-nuclear-protein recognition.
Monnot
M
M
Institut Gustave Roussy, Laboratoire de Biochimie-Enzymologie, URA 147 Centre National de la Recherche Scientifique, Villejuif, France.
Mauffret
O
O
Lescot
E
E
Fermandjian
S
S
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004611:Ellipticines / Q000737:chemistry* / Q000378:metabolism; D007364:Intercalating Agents / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism
D000970:Antineoplastic Agents; D004611:Ellipticines; D007364:Intercalating Agents; D009841:Oligonucleotides; C027767:elliptinium; D004247:DNA