2′-O,4′-C-methylene bridged nucleic acid (2′,4′-BNA):: Synthesis and triplex-forming properties

被引：152

作者：

Obika, S ^{[1
]}

Uneda, T ^{[1
]}

Sugimoto, T ^{[1
]}

Nanbu, D ^{[1
]}

Minami, T ^{[1
]}

Doi, T ^{[1
]}

Imanishi, T ^{[1
]}

机构：

[1] Osaka Univ, Grad Sch Pharmaceut Sci, Suita, Osaka 5650871, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2001年 / 9卷 / 04期

基金：

日本学术振兴会;

关键词：

D O I：

10.1016/S0968-0896(00)00325-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 tripler-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 tripler-forming oligonucleotide: (TFO) significantly enhances the binding affinity towards target dsDNA. On T, measurements. the triplex with the 2',4'-BNA oligonucleotides were found to be stabilized with DeltaT(m)/modification of +4.3 to + 5 degreesC 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-K-B transcription factor (p50)-target dsDNA binding by forming a stable tripler at pH 7.0. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：1001 / 1011

页数：11

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