title: Triple-helix formation by alpha oligodeoxynucleotides and alpha oligodeoxynucleotide-intercalator conjugates.
abstract: Base-pair sequences in double-stranded DNA can be recognized by homopyrimidine oligonucleotides that bind to the major groove at homopurine.homopyrimidine sequences thereby forming a local triple helix. To make oligodeoxynucleotides resistant to nucleases, we replaced the natural (beta) anomers of the nucleotide units by the synthetic (alpha) anomers. The 11-mer alpha oligodeoxynucleotide 5'-d(TCTCCTCCTTT)-3' binds to the major groove of DNA in an antiparallel orientation with respect to the homopurine strand, whereas a beta oligonucleotide adopts a parallel orientation. When an intercalating agent was attached to the 3' end of the alpha oligodeoxynucleotide, a strong stabilization of the triple helix was observed. A 16-base-pair homopurine.homopyrimidine sequence of human immunodeficiency virus proviral DNA was chosen as a target for a 16-mer homopyrimidine alpha oligodeoxynucleotide. A restriction enzyme that cleaves DNA at the junction of the homopurine.homopyrimidine sequence was inhibited by triple-helix formation. The 16-mer alpha oligodeoxynucleotide substituted by an intercalating agent was approximately 20 times more efficient than the unsubstituted oligomer. Nuclease-resistant alpha oligodeoxynucleotides offer additional possibilities to control gene expression at the DNA level.
authors.affiliation: Laboratoire de Biophysique, Muséum National d'Histoire Naturelle, Institut National de la Santé et de la Recherche Médicale, Paris, France.
authors.forename: J S
authors.initials: JS
authors.lastname: Sun
authors.forename: C
authors.initials: C
authors.lastname: Giovannangeli
authors.forename: J C
authors.initials: JC
authors.lastname: François
authors.forename: R
authors.initials: R
authors.lastname: Kurfurst
authors.forename: T
authors.initials: T
authors.lastname: Montenay-Garestier
authors.forename: U
authors.initials: U
authors.lastname: Asseline
authors.forename: T
authors.initials: T
authors.lastname: Saison-Behmoaras
authors.forename: N T
authors.initials: NT
authors.lastname: Thuong
authors.forename: C
authors.initials: C
authors.lastname: Hélène
mesh_terms: D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D004279:DNA, Viral / Q000737:chemistry; D006678:HIV / Q000235:genetics; D006860:Hydrogen Bonding; D007364:Intercalating Agents; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D011533:Proviruses / Q000235:genetics; D013816:Thermodynamics
chemical_list: D004279:DNA, Viral; D007364:Intercalating Agents; D009838:Oligodeoxyribonucleotides; D004247:DNA