Design of sequence-specific bifunctional nucleic acid ligands.
Homopyrimidine oligodeoxynucleotides have been covalently linked to intercalating agents. These bifunctional nucleic acid ligands bind to the major groove of DNA at homopurine.homopyrimidine sequences, where they form triple helices. The homopyrimidine oligonucleotide binds parallel to the purine strand of the double helix. Two hydrogen bonds are formed between bases of the oligonucleotide and the purines engaged in Watson-Crick base pairs. The intercalating agent inserts its aromatic ring at the triplex-duplex junction, resulting in a strong stabilization of the triple helical structure. Bifunctional oligonucleotide-intercalator conjugates provide new tools for a selective control of gene expression. In addition, irreversible reactions can be targeted to the oligonucleotide recognition sequence. Cleavage reactions can be induced by a copper-phenanthroline chelate or an ellipticine derivative covalently linked to the triple helix-forming oligonucleotide.
Laboratoire de Biophysique, INSERM U201, CNRS UA481, Muséum National d'Histoire Naturelle, Paris, France.
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Montenay-Garestier
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Hélène
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Thuong
D001483:Base Sequence; D004247:DNA / Q000378:metabolism*; D004611:Ellipticines / Q000737:chemistry / Q000378:metabolism; D007364:Intercalating Agents / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry* / Q000378:metabolism; D010618:Phenanthrolines / Q000737:chemistry / Q000378:metabolism
D004611:Ellipticines; D007364:Intercalating Agents; D009838:Oligodeoxyribonucleotides; D010618:Phenanthrolines; C034192:ellipticine; D004247:DNA; C025205:1,10-phenanthroline