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. 1993 Sep 11;21(18):4159–4165. doi: 10.1093/nar/21.18.4159

L-DNAs as potential antimessenger oligonucleotides: a reassessment.

A Garbesi 1, M L Capobianco 1, F P Colonna 1, L Tondelli 1, F Arcamone 1, G Manzini 1, C W Hilbers 1, J M Aelen 1, M J Blommers 1
PMCID: PMC310044  PMID: 8414968

Abstract

Unnatural L-2'-deoxyribonucleosides L-T, L-dC, L-dA and L-dG were prepared from L-arabinose and assembled, by solution or solid phase synthesis, to give L-oligonucleotides (L-DNAs), which contain all four natural bases. The affinity of these modified oligomers for complementary D-ribo- and D-deoxyribo-oligomers was studied with NMR, UV and CD spectroscopies and mobility shift assay on native PAGE. All experimental results indicate that L-DNAs do not, in general, recognize single-stranded, natural DNA and RNA. Hence, contrary to previous suggestions, it is not possible to envisage their use as wide scope antimessenger agents in the selective control of gene expression.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Asseline U., Hau J. F., Czernecki S., Le Diguarher T., Perlat M. C., Valery J. M., Thuong N. T. Synthesis and physicochemical properties of oligonucleotides built with either alpha-L or beta-L nucleotides units and covalently linked to an acridine derivative. Nucleic Acids Res. 1991 Aug 11;19(15):4067–4074. doi: 10.1093/nar/19.15.4067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Gagnor C., Bertrand J. R., Thenet S., Lemaître M., Morvan F., Rayner B., Malvy C., Lebleu B., Imbach J. L., Paoletti C. alpha-DNA. VI: Comparative study of alpha- and beta-anomeric oligodeoxyribonucleotides in hybridization to mRNA and in cell free translation inhibition. Nucleic Acids Res. 1987 Dec 23;15(24):10419–10436. doi: 10.1093/nar/15.24.10419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Kierzek R., He L., Turner D. H. Association of 2'-5' oligoribonucleotides. Nucleic Acids Res. 1992 Apr 11;20(7):1685–1690. doi: 10.1093/nar/20.7.1685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Morvan F., Génu C., Rayner B., Gosselin G., Imbach J. L. Sugar modified oligonucleotides. III (1). Synthesis, nuclease resistance and base pairing properties of alpha- and beta-L-octathymidylates. Biochem Biophys Res Commun. 1990 Oct 30;172(2):537–543. doi: 10.1016/0006-291x(90)90706-s. [DOI] [PubMed] [Google Scholar]
  5. Morvan F., Porumb H., Degols G., Lefebvre I., Pompon A., Sproat B. S., Rayner B., Malvy C., Lebleu B., Imbach J. L. Comparative evaluation of seven oligonucleotide analogues as potential antisense agents. J Med Chem. 1993 Jan 22;36(2):280–287. doi: 10.1021/jm00054a013. [DOI] [PubMed] [Google Scholar]
  6. Paoletti J., Bazile D., Morvan F., Imbach J. L., Paoletti C. Alpha-DNA VIII: thermodynamic parameters of complexes formed between the oligo-alpha-deoxynucleotides: alpha-d(GGAAGG) and alpha-d(CCTTCC) and their complementary oligo-beta-deoxynucleotides: beta-d(CCTTCC) and beta-d(GGAAGG) are different. Nucleic Acids Res. 1989 Apr 11;17(7):2693–2704. doi: 10.1093/nar/17.7.2693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Quadrifoglio F., Manzini G., Vasser M., Dinkelspiel K., Crea R. Conformational stability of alternating d (CG) oligomers in high salt solution. Nucleic Acids Res. 1981 May 11;9(9):2195–2206. doi: 10.1093/nar/9.9.2195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Sinha N. D., Biernat J., McManus J., Köster H. Polymer support oligonucleotide synthesis XVIII: use of beta-cyanoethyl-N,N-dialkylamino-/N-morpholino phosphoramidite of deoxynucleosides for the synthesis of DNA fragments simplifying deprotection and isolation of the final product. Nucleic Acids Res. 1984 Jun 11;12(11):4539–4557. doi: 10.1093/nar/12.11.4539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Spadari S., Maga G., Focher F., Ciarrocchi G., Manservigi R., Arcamone F., Capobianco M., Carcuro A., Colonna F., Iotti S. L-thymidine is phosphorylated by herpes simplex virus type 1 thymidine kinase and inhibits viral growth. J Med Chem. 1992 Oct 30;35(22):4214–4220. doi: 10.1021/jm00100a029. [DOI] [PubMed] [Google Scholar]
  10. Tazawa I., Tazawa S., Stempel L. M., Ts'o P. O. L'adenylyl-(3'-5')-L-adenosine and L-adenylyl-(2'-5')-L-adenosine. Biochemistry. 1970 Sep 1;9(18):3499–3514. doi: 10.1021/bi00820a003. [DOI] [PubMed] [Google Scholar]
  11. van Boeckel C. A., Visser G. M., Hegstrom R. A., van Boom J. H. Amplification of chirality based upon the association of nucleic acid strands of opposite handedness. J Mol Evol. 1987;25(2):100–105. doi: 10.1007/BF02101751. [DOI] [PubMed] [Google Scholar]

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