title: 2'-O,4'-C-Methylene bridged nucleic acid (2',4'-BNA): synthesis and triplex-forming properties.
abstract: For development of ideal antisense and antigene molecules, various chemical modifications of oligonucleotides have been studied. However, despite their importance, there is only limited information available on the triplex-forming ability of the conformationally restricted or locked oligonucleotides. We report herein that 2'-O,4'-C-methylene bridged nucleic acid (2',4'-BNA) modification of triplex-forming oligonucleotide (TFO) significantly enhances the binding affinity towards target dsDNA. On Tm measurements, the triplex with the 2',4'-BNA oligonucleotides were found to be stabilized with deltaTm/modification of +4.3 to +5 degrees C at pH 6.6 compared to the triplexes with the unmodified oligonucleotide. By means of gel-retardation assay, the binding constant of the 2',4'-BNA oligonucleotide at pH 7.0 was at least 300-fold higher than that of the natural oligonucleotide. In addition, the 2',4'-BNA oligonucleotide clearly showed the inhibition of the NF-kappaB transcription factor (p50)-target dsDNA binding by forming a stable triplex at pH 7.0.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Obika
authors.forename: T
authors.initials: T
authors.lastname: Uneda
authors.forename: T
authors.initials: T
authors.lastname: Sugimoto
authors.forename: D
authors.initials: D
authors.lastname: Nanbu
authors.forename: T
authors.initials: T
authors.lastname: Minami
authors.forename: T
authors.initials: T
authors.lastname: Doi
authors.forename: T
authors.initials: T
authors.lastname: Imanishi
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D018983:DNA Footprinting; D003850:Deoxyribonuclease I / Q000737:chemistry; D007202:Indicators and Reagents; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D007202:Indicators and Reagents; D016328:NF-kappa B; D009841:Oligonucleotides; D004247:DNA; D003850:Deoxyribonuclease I