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Chemistry of locked nucleic acids (LNA): Design, synthesis, and bio-physical properties

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Abstract

Preparation of LNA nucleosides requires a number of synthetic steps but very efficient procedures have been developed, as have protocols for synthesis of LNA oligonucleotides on automated DNA synthesizers. In all cases, LNA oligonucleotides have exhibited good aqueous solubility as would be expected from their close structural resemblance to the natural nucleic acids. The universality of LNA mediated high-affinity and specific hybridization has been demonstrated extensively with a large number of duplex forming LNA-oligonucleotides. Most importantly, most of the members of the LNA molecular family have been shown to exert their substantial affinity increase (i) in combination with standard DNA, RNA and contemporary analogues and (ii) whether inserted as single nucleosides in an oligonucleotide or as blocks of contiguous nucleotides, an important point. The works on TFO's is expanding the usefulness of LNA to double strand recognition and it has been demonstrated that LNA it is a promising structure for further base modifications in the pursuit of global sequence specific recognition of DNA.

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Authors and Affiliations

  1. Nucleic Acid Center, Department of Chemistry, University of Southern Denmark, Campusvej 55, DK-5230, Odense M, Denmark

    Jesper Wengel & Michael Petersen

  2. Santaris Pharma A/S, Bøallé 3, DK-2970, Hørsholm, Denmark

    Miriam Frieden & Troels Koch

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  1. Jesper Wengel
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  3. Miriam Frieden
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Wengel, J., Petersen, M., Frieden, M. et al. Chemistry of locked nucleic acids (LNA): Design, synthesis, and bio-physical properties. Int J Pept Res Ther 10, 237–253 (2003). https://doi.org/10.1007/s10989-004-4926-6

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