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2′,4′-Bridged Nucleic Acids Containing Plural Heteroatoms in the Bridge Moiety

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Synthesis of Therapeutic Oligonucleotides

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Abstract

Bridge modifications between the 2′- and 4′-positions of a nucleoside have attracted much attention for improving properties of nucleic acid drugs, and many classes of 2′,4′-bridged nucleic acids have been developed to date. Evaluation of oligonucleotides containing 2′,4′-bridged nucleic acids suggests that, in addition to the bridge size, the number, type, and position of atoms composing the bridge unit affect (i) the binding affinity to target nucleic acid, (ii) resistance against nuclease degradation, and other factors. The addition of plural heteroatoms is an attractive bridge modification because interaction of the heteroatom with water can affect the properties of the oligonucleotides. In this chapter, focusing on 2′,4′-bridged nucleic acids containing plural heteroatoms in the bridge moiety, we mainly describe the design concept and synthesis. In addition, properties of 2′,4′-bridged nucleic acids are briefly explained.

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan

    Yoshiyuki Hari

  2. Osaka University, Suita, Osaka, Japan

    Satoshi Obika

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  1. Yoshiyuki Hari
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  2. Satoshi Obika
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Correspondence to Yoshiyuki Hari .

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  1. Osaka University, Suita, Osaka, Japan

    Satoshi Obika

  2. Tokyo Institute of Technology, Yokohama, Kanagawa, Japan

    Mitsuo Sekine

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Hari, Y., Obika, S. (2018). 2′,4′-Bridged Nucleic Acids Containing Plural Heteroatoms in the Bridge Moiety. In: Obika, S., Sekine, M. (eds) Synthesis of Therapeutic Oligonucleotides. Springer, Singapore. https://doi.org/10.1007/978-981-13-1912-9_12

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