The eight stereoisomers of LNA (locked nucleic acid): A remarkable family of strong RNA binding molecules

Angewandte Chemie (International Edition in English)

Volumn 39, Issue 9, 2000, Pages

  Rajwanshi, Vivek K ^a   Håkansson, Anders E ^a   Sørensen, Mads D ^a   Pitsch, Stefan ^b   Singh, Sanjay K ^a   Kumar, Ravindra ^a   Nielsen, Poul ^c   Wengel, Jesper ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b ETH ZURICH   (Switzerland)

^c UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

NUCLEIC ACID; RNA BINDING PROTEIN;

ARTICLE; CHEMICAL MODIFICATION; CHEMICAL STRUCTURE; RNA BINDING; STEREOISOMERISM; SYNTHESIS;

EID: 0034595242     PISSN: 05700833     EISSN: None     Source Type: Journal    
DOI: 10.1002/(sici)1521-3773(20000502)39:9<1656::aid-anie1656>3.0.co;2-q     Document Type: Article

References (25)

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10. c) A. A. Koshkin, P. Nielsen, M. Meldgaard, V. K. Rajwanshi, S. K. Singh, J. Wengel, J. Am. Chem. Soc. 1998, 120, 13252.
11. We have defined LNA as an oligonucleotide containing one or more 2′-O,4′-C-methylene-β-D-ribofuranosyl nucleotide monomer(s). The natural β-D-ribo configuration is generally assigned to LNA (and LNA monomers) as the positioning of the 1-nitrogen and 2′-, 3′-, and 5′-oxygen atoms are equivalent to the one found in RNA. Similar considerations apply for the other LNA stereoisomers. It should be noted that the formation of LNA derivatives of arabino and lyxo configuration is precluded because of the inherent syn-positioning of the 2′-oxygen and 5′-carbon atoms.
12. S. Obika, D. Nanbu, Y. Hari, J. Andoh, K. Morio, T. Doi, T. Imanishi, Tetrahedron Lett. 1998, 39, 5401.
13. a) V. K. Rajwanshi, A. E. Håkansson, B. M. Dahl, J. Wengel, Chem. Commun. 1999, 1395;
14. b) V. K. Rajwanshi, A. E. Håkansson, R. Kumar, J. Wengel, Chem. Commun. 1999, 2073.
15. All LNA stereoisomers have been synthesized on an automated DNA synthesizer using phosphoramidite chemistry; see: M. H. Caruthers, Acc. Chem. Res. 1991, 24, 278. The phosphoramidite derivatives necessary for incorporation of the four LNA monomers were synthesized from the corresponding 5′-O-(4,4′-dimethoxy)trityl protected 1-(2-O,4-C-methylene-pentofuranosyl)thymine derivatives (see references [3b] and [6]). The synthesis of the α-L-xylo-LNA nucleosides and oligonucleotides will be published elsewhere. The homo-thymine LNAs were synthesized on commercially available T-supports but are described as "fully modified" herein. The composition of the LNAs was confirmed by MALDI mass spectrometry and the purity (> 90%) by capillary gel electrophoresis.
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18. m value > 90°C in the medium salt buffer was ruled out as no transition was observed in either a low salt buffer (experiment run from 10°C to 90°C) nor towards the mismatched RNA targets.
19. C. Hendrix, H. Rosemeyer, I. Verheggen, F. Seela, A. Van Aerschot, P. Herdewijn, Chem. Eur. J. 1997, 3, 110.
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21. M. Raunkjær, C. E. Olsen, J. Wengel, J. Chem. Soc. Perkin Trans. 1 1999, 2543.
22. Rotations around the C-1′/N-1 and C-4′/C-5′ bonds are expected to be energetically straightforward. This allows a close overlap between the two 5′-oxygen atoms and the two thymine bases, not indicated in Figure 4.
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24. It should be noted that β-L-ribofuranosyl nucleic acids have been shown to hybridize efficiently with complementary RNA; see reference [8a]; S. Fujimori, K. Shudo, J. Am. Chem. Soc. 1990, 112, 7436. Also, β-D-arabinofuranosyl nucleic acids hybridize towards complementary RNA, see M. J. Damha, C. J. Wilds, A. Noronha, I. Brukner, G. Borkow, D. Arion, M. A. Parniak, J. Am. Chem. Soc. 1998, 120, 12976, and references therein.
25. It should be noted that β-L-ribofuranosyl nucleic acids have been shown to hybridize efficiently with complementary RNA; see reference [8a]; S. Fujimori, K. Shudo, J. Am. Chem. Soc. 1990, 112, 7436. Also, β-D-arabinofuranosyl nucleic acids hybridize towards complementary RNA, see M. J. Damha, C. J. Wilds, A. Noronha, I. Brukner, G. Borkow, D. Arion, M. A. Parniak, J. Am. Chem. Soc. 1998, 120, 12976, and references therein.