Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1996 Aug 1;24(15):2974–2980. doi: 10.1093/nar/24.15.2974

Oligodeoxynucleotides containing C-7 propyne analogs of 7-deaza-2'-deoxyguanosine and 7-deaza-2'-deoxyadenosine.

C A Buhr 1, R W Wagner 1, D Grant 1, B C Froehler 1
PMCID: PMC146038  PMID: 8760882

Abstract

The synthesis, hybridization properties and antisense activities of oligodeoxynucleotides (ODNs) containing 7-(1-propynyl)-7-deaza-2'-deoxyguanosine (pdG) and 7-(1-propynyl)-7-deaza-2'-deoxyadenosine (pdA) are described. The suitably protected nucleosides were synthesized and incorporated into ODNs. Thermal denaturation (Tm) of these ODNs hybridized to RNA demonstrates an increased stability relative to 7-unsubstituted deazapurine and unmodified ODN controls. Antisense inhibition by these ODNs was determined in a controlled microinjection assay and the results demonstrate that an ODN containing pdG is approximately 6 times more active than the unmodified ODN. 7-Propyne-7-deaza-2'-deoxyguanosine is a promising lead analog for the development of antisense ODNs with increased potency.

Full Text

The Full Text of this article is available as a PDF (96.3 KB).

Selected References

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

  1. Bennett C. F., Chiang M. Y., Chan H., Shoemaker J. E., Mirabelli C. K. Cationic lipids enhance cellular uptake and activity of phosphorothioate antisense oligonucleotides. Mol Pharmacol. 1992 Jun;41(6):1023–1033. [PubMed] [Google Scholar]
  2. Bennett C. F., Condon T. P., Grimm S., Chan H., Chiang M. Y. Inhibition of endothelial cell adhesion molecule expression with antisense oligonucleotides. J Immunol. 1994 Apr 1;152(7):3530–3540. [PubMed] [Google Scholar]
  3. Colige A., Sokolov B. P., Nugent P., Baserga R., Prockop D. J. Use of an antisense oligonucleotide to inhibit expression of a mutated human procollagen gene (COL1A1) in transfected mouse 3T3 cells. Biochemistry. 1993 Jan 12;32(1):7–11. doi: 10.1021/bi00052a002. [DOI] [PubMed] [Google Scholar]
  4. Dean N. M., McKay R., Condon T. P., Bennett C. F. Inhibition of protein kinase C-alpha expression in human A549 cells by antisense oligonucleotides inhibits induction of intercellular adhesion molecule 1 (ICAM-1) mRNA by phorbol esters. J Biol Chem. 1994 Jun 10;269(23):16416–16424. [PubMed] [Google Scholar]
  5. Froehler B. C., Matteucci M. D. Dialkylformamidines: depurination resistant N6-protecting group for deoxyadenosine. Nucleic Acids Res. 1983 Nov 25;11(22):8031–8036. doi: 10.1093/nar/11.22.8031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Froehler B. C. Oligodeoxynucleotide synthesis. H-phosphonate approach. Methods Mol Biol. 1993;20:63–80. doi: 10.1385/0-89603-281-7:63. [DOI] [PubMed] [Google Scholar]
  7. Lewis J. G., Lin K. Y., Kothavale A., Flanagan W. M., Matteucci M. D., DePrince R. B., Mook R. A., Jr, Hendren R. W., Wagner R. W. A serum-resistant cytofectin for cellular delivery of antisense oligodeoxynucleotides and plasmid DNA. Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3176–3181. doi: 10.1073/pnas.93.8.3176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lyon P. A., Reese C. B. The structures of di-N-aroyl derivatives of adenosine and 2-aminopyridine. J Chem Soc Perkin 1. 1974;(23):2645–2649. [PubMed] [Google Scholar]
  9. Milligan J. F., Krawczyk S. H., Wadwani S., Matteucci M. D. An anti-parallel triple helix motif with oligodeoxynucleotides containing 2'-deoxyguanosine and 7-deaza-2'-deoxyxanthosine. Nucleic Acids Res. 1993 Jan 25;21(2):327–333. doi: 10.1093/nar/21.2.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Moulds C., Lewis J. G., Froehler B. C., Grant D., Huang T., Milligan J. F., Matteucci M. D., Wagner R. W. Site and mechanism of antisense inhibition by C-5 propyne oligonucleotides. Biochemistry. 1995 Apr 18;34(15):5044–5053. doi: 10.1021/bi00015a015. [DOI] [PubMed] [Google Scholar]
  11. Prober J. M., Trainor G. L., Dam R. J., Hobbs F. W., Robertson C. W., Zagursky R. J., Cocuzza A. J., Jensen M. A., Baumeister K. A system for rapid DNA sequencing with fluorescent chain-terminating dideoxynucleotides. Science. 1987 Oct 16;238(4825):336–341. doi: 10.1126/science.2443975. [DOI] [PubMed] [Google Scholar]
  12. Reese C. B., Zard L. Some observations relating to the oximate ion promoted unblocking of oligonucleotide aryl esters. Nucleic Acids Res. 1981 Sep 25;9(18):4611–4626. doi: 10.1093/nar/9.18.4611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Seela F., Driller H. Palindromic oligonucleotides containing 7-deaza-2'-deoxyguanosine: solid-phase synthesis of d[(p)GG*AATTCC] octamers and recognition by the endodeoxyribonuclease EcoRI. Nucleic Acids Res. 1986 Mar 11;14(5):2319–2332. doi: 10.1093/nar/14.5.2319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Seela F., Kehne A. Palindromic octa- and dodecanucleotides containing 2'-deoxytubercidin: synthesis, hairpin formation, and recognition by the endodeoxyribonuclease EcoRI. Biochemistry. 1987 Apr 21;26(8):2232–2238. doi: 10.1021/bi00382a024. [DOI] [PubMed] [Google Scholar]
  15. Wagner R. W., Matteucci M. D., Lewis J. G., Gutierrez A. J., Moulds C., Froehler B. C. Antisense gene inhibition by oligonucleotides containing C-5 propyne pyrimidines. Science. 1993 Jun 4;260(5113):1510–1513. doi: 10.1126/science.7684856. [DOI] [PubMed] [Google Scholar]

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

RESOURCES