Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1997 Dec 15;25(24):4954–4961. doi: 10.1093/nar/25.24.4954

Inhibitory properties of double-helix-forming circular oligonucleotides.

E Azhayeva 1, A Azhayev 1, S Auriola 1, U Tengvall 1, A Urtti 1, Lönnberg 1
PMCID: PMC147146  PMID: 9396802

Abstract

Several circular oligonucleotides were synthesized and characterized by electrospray ionization mass spectrometry. Experiments on termination of primer extension catalysed by DNA polymerases, Klenow fragment and Tth have demonstrated that a double helix forming circular 2'-deoxyribooligomer containing a 25mer sequence complementary to the target single-stranded DNA along with a 34mer random mismatching stretch appears to be a potent inhibitor of replication in vitro. Studies on inhibition of luciferase gene expression in a cell-free transcription-translation system have shown that a duplex forming circular 2'-deoxyribooligonucleotide containing a 25mer sequence complementary to the target mRNA and a 14mer random mismatching stretch can serve as an effective antisense compound as a standard linear complementary oligomer. Features of double helix forming circular oligonucleotides composed of 2'-deoxyribonucleosides seem to be useful for the design of new antigene and antisense agents.

Full Text

The Full Text of this article is available as a PDF (191.3 KB).

Selected References

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

  1. Azhayeva E., Azhayev A., Guzaev A., Hovinen J., Lönnberg H. Looped oligonucleotides form stable hybrid complexes with a single-stranded DNA. Nucleic Acids Res. 1995 Apr 11;23(7):1170–1176. doi: 10.1093/nar/23.7.1170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Azhayeva E., Azhayev A., Guzaev A., Lönnberg H. Selective binding of looped oligonucleotides to a single-stranded DNA and its influence on replication in vitro. Nucleic Acids Res. 1995 Nov 11;23(21):4255–4261. doi: 10.1093/nar/23.21.4255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Crooke S. T., Bennett C. F. Progress in antisense oligonucleotide therapeutics. Annu Rev Pharmacol Toxicol. 1996;36:107–129. doi: 10.1146/annurev.pa.36.040196.000543. [DOI] [PubMed] [Google Scholar]
  4. Fedorova O. A., Gottikh M. V., Romanova E. A., Oretskaia T. S., Dolinnaia N. G., Shabarova Z. A. Tsiklicheskie oligonukleotidy. Gibridizatsionnye svoistva i sposobnost' vyzyvat' rasshcheplenie RNK RNKazoi H. Mol Biol (Mosk) 1995 Sep-Oct;29(5):1161–1167. [PubMed] [Google Scholar]
  5. Ghosh M. K., Cohen J. S. Oligodeoxynucleotides as antisense inhibitors of gene expression. Prog Nucleic Acid Res Mol Biol. 1992;42:79–126. doi: 10.1016/s0079-6603(08)60574-7. [DOI] [PubMed] [Google Scholar]
  6. Greig M., Griffey R. H. Utility of organic bases for improved electrospray mass spectrometry of oligonucleotides. Rapid Commun Mass Spectrom. 1995;9(1):97–102. doi: 10.1002/rcm.1290090121. [DOI] [PubMed] [Google Scholar]
  7. Guzaev A. P. An efficient synthesis of 3'-mercaptoalkylated oligodeoxyribonucleotides on the universal solid support. Nucleic Acids Symp Ser. 1991;(24):236–236. [PubMed] [Google Scholar]
  8. Hacia J. G., Dervan P. B., Wold B. J. Inhibition of Klenow fragment DNA polymerase on double-helical templates by oligonucleotide-directed triple-helix formation. Biochemistry. 1994 May 24;33(20):6192–6200. doi: 10.1021/bi00186a019. [DOI] [PubMed] [Google Scholar]
  9. Kogoma T., Subia N. L., von Meyenburg K. Function of ribonuclease H in initiation of DNA replication in Escherichia coli K-12. Mol Gen Genet. 1985;200(1):103–109. doi: 10.1007/BF00383320. [DOI] [PubMed] [Google Scholar]
  10. Lamond A. I., Sproat B. S. Antisense oligonucleotides made of 2'-O-alkylRNA: their properties and applications in RNA biochemistry. FEBS Lett. 1993 Jun 28;325(1-2):123–127. doi: 10.1016/0014-5793(93)81427-2. [DOI] [PubMed] [Google Scholar]
  11. Potier N., Van Dorsselaer A., Cordier Y., Roch O., Bischoff R. Negative electrospray ionization mass spectrometry of synthetic and chemically modified oligonucleotides. Nucleic Acids Res. 1994 Sep 25;22(19):3895–3903. doi: 10.1093/nar/22.19.3895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Samadashwily G. M., Mirkin S. M. Trapping DNA polymerases using triplex-forming oligodeoxyribonucleotides. Gene. 1994 Nov 4;149(1):127–136. doi: 10.1016/0378-1119(94)90421-9. [DOI] [PubMed] [Google Scholar]
  13. Stull R. A., Zon G., Szoka F. C., Jr An in vitro messenger RNA binding assay as a tool for identifying hybridization-competent antisense oligonucleotides. Antisense Nucleic Acid Drug Dev. 1996 Fall;6(3):221–228. doi: 10.1089/oli.1.1996.6.221. [DOI] [PubMed] [Google Scholar]
  14. Yamakawa H., Hosono K., Ishibashi T., Takai K., Takaku H. Properties of nicked and circular dumbbell RNA-DNA chimeric oligonucleotides. Nucleic Acids Symp Ser. 1995;(34):133–134. [PubMed] [Google Scholar]

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

RESOURCES