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Bridged nucleic acids (BNAs) are modified RNA nucleotides. They are sometimes also referred to as constrained or inaccessible RNA molecules. BNA monomers can contain a five-membered, six-membered or even a seven-membered bridged structure with a “fixed” C3’-endo sugar puckering.〔Saenger, W. (1984) ''Principles of Nucleic Acid Structure'', Springer-Verlag, New York, ISBN ISBN 3-540-90761-0.〕 The bridge is synthetically incorporated at the 2’, 4’-position of the ribose to afford a 2’, 4’-BNA monomer. The monomers can be incorporated into oligonucleotide polymeric structures using standard phosphoamidite chemistry. BNAs are structurally rigid oligo-nucleotides with increased binding affinities and stability. == Chemical structures == Chemical structures of BNA monomers containing a bridge at the 2’, 4’-position of the ribose to afford a 2’, 4’-BNA monomer as synthesized by Takeshi Imanishi’s group.〔 〕 The nature of the bridge can vary for different types of monomers. The 3D structures for A-RNA and B-DNA were used as a template for the design of the BNA monomers. The goal for the design was to find derivatives that possess high binding affinities with complementary RNA and/or DNA strands. The presence of 2’-hydroxyls in the RNA backbone favors a structure that resembles the A-form structure of DNA. The flexible five-membered furanose ring in nucleotides exists in equilibrium of two preferred conformations of the N- (C3’-endo, A-form) and the S-type (C2’-endo, B-form) as illustrated in the next figure. An increased conformational inflexibility of the sugar moiety in nucleosides (oligonucleotides) results in a gain of high binding affinity with complementary single-stranded RNA and/or double-stranded DNA. The first 2’,4’-BNA (LNA) monomers were first synthesized by Takeshi Imanishi’s group in 1997〔 followed independently by Jesper Wengel’s group in 1998. Chemical structures of other BNAs that were synthesized in the past years as indicated below the structures. BNA nucleotides can be incorporated into DNA or RNA oligonucleotides at any desired position. Such oligomers are synthesized chemically and are now commercially available. The bridged ribose conformation enhances base stacking and pre-organizes the backbone of the oligonucleotide significantly increasing their hybridization properties. The incorporation of BNAs into oligonucleotides allows the production of modified synthetic oligonucleotides with: *Equal or higher binding affinity against an DNA or RNA complement with excellent single-mismatch discriminating power, *Better RNA selective binding, *Stronger and more sequence selective triplex-forming characters, and *Pronounced higher nuclease resistance, even higher than Sp-phosphorthioate analogues, *Good aqueous solubility of the resulting oligonucleotides when compared to regular DNA or RNA oligonucleotides. Chemical structures of BNAs were introduced in 2007 by Imanishi’s group.〔 These new generation of BNAs analogues are called 2’,4’-BNANC(), 2’,4’-BNANC(), and 2’,4’-BNANC(). New BNA analogs introduced by Imanishi’s group were designed by taking the length of the bridged moiety into account. A six-membered bridged structure with a unique structural feature (N-O bond) in the sugar moiety was designed to have a nitrogen atom. This atom improves the formation of duplexes and triplexes by lowering the repulsion between the negatively charged backbone phosphates. These modifications allow to control the affinity towards complementary strands, regulate resistance against nuclease degradation and the synthesis of functional molecules designed for specific applications in genomics. The properties of these analogs were investigated and compared to those of previous 2’,4’-BNA (LNA) modified oligonucleotides by Imanishi’s group. Imanishi’s results show that “2’,4’-BNANC-modified oligonucleotides with these profiles show great promise for applications in antisense and antigene technologies.” Makoto Koizumi in 2004 reviewed the properties of BNAs with focus on ENAs as antisense and antigen oligonucleotides (AONs) and proposed an action mechanism for these compounds that may involve translation arrest, mRNA degradation mediated by RNase H and splicing arrest. This is illustrated in the following figure. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Bridged nucleic acid」の詳細全文を読む スポンサード リンク
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