2'-O,4'-C-Methylene bridged nucleic acid (2',4'-BNA): synthesis and triplex-forming properties.

作者: Satoshi Obika , Takeshi Uneda , Tomomi Sugimoto , Daishu Nanbu , Takashi Minami

DOI: 10.1016/S0968-0896(00)00325-4

关键词: ChemistryBinding constantMoleculeMethyleneChemical synthesisBicyclic moleculeStereochemistryOligonucleotideBiological activityBiochemistryBridged nucleic acid

摘要: Abstract For development of ideal antisense and antigene molecules, various chemical modifications oligonucleotides have been studied. However, despite their importance, there is only limited information available on the triplex-forming ability conformationally restricted or locked oligonucleotides. We report herein that 2′-O,4′-C-methylene bridged nucleic acid (2′,4′-BNA) modification oligonucleotide (TFO) significantly enhances binding affinity towards target dsDNA. On Tm measurements, triplex with 2′,4′-BNA were found to be stabilized ΔTm/modification +4.3 +5 °C at pH 6.6 compared triplexes unmodified oligonucleotide. By means gel-retardation assay, constant 7.0 was least 300-fold higher than natural In addition, clearly showed inhibition NF-κB transcription factor (p50)-target dsDNA by forming a stable 7.0.

参考文章(51)
Alexei A. Koshkin, Sanjay K. Singh, Poul Nielsen, Vivek K. Rajwanshi, Ravindra Kumar, Michael Meldgaard, Carl Erik Olsen, Jesper Wengel, LNA (Locked Nucleic Acids): Synthesis of the adenine, cytosine, guanine, 5-methylcytosine, thymine and uracil bicyclonucleoside monomers, oligomerisation, and unprecedented nucleic acid recognition Tetrahedron. ,vol. 54, pp. 3607- 3630 ,(1998) , 10.1016/S0040-4020(98)00094-5
Satoshi Obika, Ken-ichiro Morio, Yoshiyuki Hari, Takeshi Imanishi, Preparation and properties of 2′,5′-linked oligonucleotide analogues containing 3′-O,4′-C-methyleneribonucleosides Bioorganic & Medicinal Chemistry Letters. ,vol. 9, pp. 515- 518 ,(1999) , 10.1016/S0960-894X(99)00028-1
Alexei A. Koshkin, Vivek K. Rajwanshi, Jesper Wengel, Novel convenient syntheses of LNA [2.2.1]bicyclo nucleosides Tetrahedron Letters. ,vol. 39, pp. 4381- 4384 ,(1998) , 10.1016/S0040-4039(98)00706-0
Juan Luis Asensio, Reuben Carr, Tom Brown, Andrew N. Lane, CONFORMATIONAL AND THERMODYNAMIC PROPERTIES OF PARALLEL INTRAMOLECULAR TRIPLE HELICES CONTAINING A DNA, RNA, OR 2'-OMEDNA THIRD STRAND Journal of the American Chemical Society. ,vol. 121, pp. 11063- 11070 ,(1999) , 10.1021/JA991949S
Satoshi Obika, Ken-ichiro Morio, Yoshiyuki Hari, Takeshi Imanishi, Facile synthesis and conformation of 3′-O,4′-C-methyleneribonucleosides Chemical Communications. pp. 2423- 2424 ,(1999) , 10.1039/A907218G
Keith Fox, Targeting DNA with Triplexes Current Medicinal Chemistry. ,vol. 7, pp. 17- 37 ,(2000) , 10.2174/0929867003375506
Satoshi Obika, Daishu Nanbu, Yoshiyuki Hari, Jun-ichi Andoh, Ken-ichiro Morio, Takefumi Doi, Takeshi Imanishi, Stability and structural features of the duplexes containing nucleoside analogues with a fixed N-type conformation, 2′-O,4′-C-methyleneribonucleosides Tetrahedron Letters. ,vol. 39, pp. 5401- 5404 ,(1998) , 10.1016/S0040-4039(98)01084-3
Patrick A. Baeuerle, The inducible transcription activator NF-κB: regulation by distinct protein subunits Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. ,vol. 1072, pp. 63- 80 ,(1991) , 10.1016/0304-419X(91)90007-8