Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1994 Mar 11;22(5):703–710. doi: 10.1093/nar/22.5.703

Incorporation of (R)- and (S)-3',4'-seco-thymidine into oligodeoxynucleotides: hybridization properties and enzymatic stability.

P Nielsen 1, F Kirpekar 1, J Wengel 1
PMCID: PMC307872  PMID: 8139908

Abstract

Novel flexible oligodeoxynucleotide analogues containing (R)- and (S)-3',4'-seco-thymidine were synthesized on an automated DNA-synthesizer using the phosphoramidite approach. Oligodeoxynucleotide analogues (17-mers) having one or three modifications in the middle or one or two modifications in the ends were evaluated with respect to hybridization properties and enzymatic stability. 3'-End-modified oligomers were stable towards 3'-exonuclease degradation and displayed acceptable hybridization properties.

Full text

PDF
707

Images in this article

707Image
on p.707
707Image
on p.707

Selected References

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

  1. Augustyns K., Van Aerschot A., Van Schepdael A., Urbanke C., Herdewijn P. Influence of the incorporation of (S)-9-(3,4-dihydroxybutyl)adenine on the enzymatic stability and base-pairing properties of oligodeoxynucleotides. Nucleic Acids Res. 1991 May 25;19(10):2587–2593. doi: 10.1093/nar/19.10.2587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Augustyns K., Vandendriessche F., Van Aerschot A., Busson R., Urbanke C., Herdewijn P. Incorporation of hexose nucleoside analogues into oligonucleotides: synthesis, base-pairing properties and enzymatic stability. Nucleic Acids Res. 1992 Sep 25;20(18):4711–4716. doi: 10.1093/nar/20.18.4711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bellon L., Barascut J. L., Maury G., Divita G., Goody R., Imbach J. L. 4'-Thio-oligo-beta-D-ribonucleotides: synthesis of beta-4'-thio-oligouridylates, nuclease resistance, base pairing properties, and interaction with HIV-1 reverse transcriptase. Nucleic Acids Res. 1993 Apr 11;21(7):1587–1593. doi: 10.1093/nar/21.7.1587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bjergårde K., Dahl O. Solid phase synthesis of oligodeoxyribonucleoside phosphorodithioates from thiophosphoramidites. Nucleic Acids Res. 1991 Nov 11;19(21):5843–5850. doi: 10.1093/nar/19.21.5843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hoke G. D., Draper K., Freier S. M., Gonzalez C., Driver V. B., Zounes M. C., Ecker D. J. Effects of phosphorothioate capping on antisense oligonucleotide stability, hybridization and antiviral efficacy versus herpes simplex virus infection. Nucleic Acids Res. 1991 Oct 25;19(20):5743–5748. doi: 10.1093/nar/19.20.5743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hoke G. D., Draper K., Freier S. M., Gonzalez C., Driver V. B., Zounes M. C., Ecker D. J. Effects of phosphorothioate capping on antisense oligonucleotide stability, hybridization and antiviral efficacy versus herpes simplex virus infection. Nucleic Acids Res. 1991 Oct 25;19(20):5743–5748. doi: 10.1093/nar/19.20.5743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Huth-Fehre T., Gosine J. N., Wu K. J., Becker C. H. Matrix-assisted laser desorption mass spectrometry of oligodeoxythymidylic acids. Rapid Commun Mass Spectrom. 1992 Mar;6(3):209–213. doi: 10.1002/rcm.1290060312. [DOI] [PubMed] [Google Scholar]
  8. Marcus-Sekura C. J., Woerner A. M., Shinozuka K., Zon G., Quinnan G. V., Jr Comparative inhibition of chloramphenicol acetyltransferase gene expression by antisense oligonucleotide analogues having alkyl phosphotriester, methylphosphonate and phosphorothioate linkages. Nucleic Acids Res. 1987 Jul 24;15(14):5749–5763. doi: 10.1093/nar/15.14.5749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Marshall W. S., Caruthers M. H. Phosphorodithioate DNA as a potential therapeutic drug. Science. 1993 Mar 12;259(5101):1564–1570. doi: 10.1126/science.7681216. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Morvan F., Rayner B., Imbach J. L., Chang D. K., Lown J. W. alpha-DNA. I. Synthesis, characterization by high field 1H-NMR, and base-pairing properties of the unnatural hexadeoxyribonucleotide alpha-[d(CpCpTpTpCpC)] with its complement beta-[d(GpGpApApGpG)]. Nucleic Acids Res. 1986 Jun 25;14(12):5019–5035. doi: 10.1093/nar/14.12.5019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Newman P. C., Nwosu V. U., Williams D. M., Cosstick R., Seela F., Connolly B. A. Incorporation of a complete set of deoxyadenosine and thymidine analogues suitable for the study of protein nucleic acid interactions into oligodeoxynucleotides. Application to the EcoRV restriction endonuclease and modification methylase. Biochemistry. 1990 Oct 23;29(42):9891–9901. doi: 10.1021/bi00494a020. [DOI] [PubMed] [Google Scholar]
  13. Perbost M., Lucas M., Chavis C., Pompon A., Baumgartner H., Rayner B., Griengl H., Imbach J. L. Sugar modified oligonucleotides. I. Carbo-oligodeoxynucleotides as potential antisense agents. Biochem Biophys Res Commun. 1989 Dec 15;165(2):742–747. doi: 10.1016/s0006-291x(89)80029-4. [DOI] [PubMed] [Google Scholar]
  14. Perbost M., Lucas M., Chavis C., Pompon A., Baumgartner H., Rayner B., Griengl H., Imbach J. L. Sugar modified oligonucleotides. I. Carbo-oligodeoxynucleotides as potential antisense agents. Biochem Biophys Res Commun. 1989 Dec 15;165(2):742–747. doi: 10.1016/s0006-291x(89)80029-4. [DOI] [PubMed] [Google Scholar]
  15. Pieles U., Zürcher W., Schär M., Moser H. E. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry: a powerful tool for the mass and sequence analysis of natural and modified oligonucleotides. Nucleic Acids Res. 1993 Jul 11;21(14):3191–3196. doi: 10.1093/nar/21.14.3191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Scheiner P., Geer A., Bucknor A. M., Imbach J. L., Schinazi R. F. Acyclic analogues of 3'-azido-3'-deoxythymidine as potential antiviral agents. Nucleoside synthesis by Michael addition. J Med Chem. 1989 Jan;32(1):73–76. doi: 10.1021/jm00121a015. [DOI] [PubMed] [Google Scholar]
  17. Shaw J. P., Kent K., Bird J., Fishback J., Froehler B. Modified deoxyoligonucleotides stable to exonuclease degradation in serum. Nucleic Acids Res. 1991 Feb 25;19(4):747–750. doi: 10.1093/nar/19.4.747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Sproat B. S., Beijer B., Iribarren A. New synthetic routes to protected purine 2'-O-methylriboside-3'-O-phosphoramidites using a novel alkylation procedure. Nucleic Acids Res. 1990 Jan 11;18(1):41–49. doi: 10.1093/nar/18.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Stein C. A., Cohen J. S. Oligodeoxynucleotides as inhibitors of gene expression: a review. Cancer Res. 1988 May 15;48(10):2659–2668. [PubMed] [Google Scholar]
  20. Wittenburg E. Synthese der anomeren Thymin-nucleoside der 2-Desoxy-D-ribopyranose. Chem Ber. 1968;101(5):1614–1625. doi: 10.1002/cber.19681010510. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES