Skip to main content
PMC home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1986 Apr 25;14(8):3449–3462. doi: 10.1093/nar/14.8.3449

Modified polynucleotides. VII. Impaired integrity of a synthetic DNA containing the antiherpetic agent 5-isopropyl-2'-deoxyuridine.

J Sági, A Szabolcs, A Szemźó, L Otvös
PMCID: PMC339784  PMID: 3703679

Abstract

5-Isopropyl-2'-deoxyuridine (ip5dU) was recently recognized as a clinically useful antiherpetic (HSV-1) agent. An ip5dU-containing polynucleotide, poly (dA-dT, ip5dU) was prepared to study how physical and bio-organic properties of the synthetic DNA model poly (dA-dT) would change upon partial substitution of thymidine. Synthesis was carried out with DNA polymerase enzyme and the polymers contained 7-9% of ip5dU. It proved to be less thermostable than poly (dA-dT) and the transition width was highly increased. Although it was a very efficient template for DNA polymerase enzyme, template activity for RNA synthesis was strongly reduced by the presence of ip5dU. Diminished stability against enzymic degradation, especially against single-strand-specific Nuclease S1 was also observed.

Full text

PDF
3453

Selected References

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

  1. Allaudeen H. S., Chen M. S., Lee J. J., De Clercq E., Prusoff W. H. Incorporation of E-5-(2-halovinyl)-2'-deoxyuridines into deoxyribonucleic acids of herpes simplex virus type 1-infected cells. J Biol Chem. 1982 Jan 25;257(2):603–606. [PubMed] [Google Scholar]
  2. De Clercq E. Biochemical aspects of the selective antiherpes activity of nucleoside analogues. Biochem Pharmacol. 1984 Jul 15;33(14):2159–2169. doi: 10.1016/0006-2952(84)90649-x. [DOI] [PubMed] [Google Scholar]
  3. De Clercq E., Walker R. T. Synthesis and antiviral properties of 5-vinylpyrimidine nucleoside analogs. Pharmacol Ther. 1984;26(1):1–44. doi: 10.1016/0163-7258(84)90049-4. [DOI] [PubMed] [Google Scholar]
  4. Kowalzick L., Gauri K. K., Spadari S., Pedrali-Noy G., Koch G. Differential substrate specificity of DNA polymerase beta and of a DNA polymerase induced by herpes simplex virus type 2 towards thymidine triphosphate analogues. J Gen Virol. 1984 Mar;65(Pt 3):467–475. doi: 10.1099/0022-1317-65-3-467. [DOI] [PubMed] [Google Scholar]
  5. Kowalzick L., Gauri K. K., Spadari S., Pedrali-Noy G., Kühne J., Koch G. Differential incorporation of thymidylate analogues into DNA by DNA polymerase alpha and by DNA polymerases specified by two herpes simplex viruses. J Gen Virol. 1982 Sep;62(Pt 1):29–38. doi: 10.1099/0022-1317-62-1-29. [DOI] [PubMed] [Google Scholar]
  6. Mancini W. R., De Clercq E., Prusoff W. H. The relationship between incorporation of E-5-(2-Bromovinyl)-2'-deoxyuridine into herpes simplex virus type 1 DNA with virus infectivity and DNA integrity. J Biol Chem. 1983 Jan 25;258(2):792–795. [PubMed] [Google Scholar]
  7. Misra V., Nelson R. C., Babiuk L. A. Inhibition of glycosylation of bovine herpesvirus 1 glycoproteins by the thymidine analog (E)-5-(2 Bromovinyl)-2'-deoxyuridine. Antimicrob Agents Chemother. 1983 Jun;23(6):857–865. doi: 10.1128/aac.23.6.857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Siegel S. A., Otto M. J., De Clercq E., Prusoff W. H. Effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine on synthesis of herpes simplex virus type 1-specific polypeptides. Antimicrob Agents Chemother. 1984 May;25(5):566–570. doi: 10.1128/aac.25.5.566. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Sági J. T., Szabolcs A., Szemzö A., Otvös L. Modified polynucleotides. I. Investigation of the enzymatic polymerization of 5-alkyl-dUTP-s. Nucleic Acids Res. 1977 Aug;4(8):2767–2777. doi: 10.1093/nar/4.8.2767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Sági J., Brahms S., Brahms J., Otvös L. Effect of 5-alkyl substitution of uracil on the thermal stability of poly [d(A-r5U)] copolymers. Nucleic Acids Res. 1979 Jun 25;6(8):2839–2848. doi: 10.1093/nar/6.8.2839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Sági J., Czuppon A., Kajtár M., Szabolcs A., Szemzö A., Otvös L. Modified polynucleotides. VI. Properties of a synthetic DNA containing the anti-herpes agent (E)-5-(2-bromovinyl)-2'-deoxyuridine. Nucleic Acids Res. 1982 Oct 11;10(19):6051–6066. doi: 10.1093/nar/10.19.6051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Sági J., Nowak R., Zmudzka B., Szemzö A., Otvös L. A study of substrate specificity of mammalian and bacterial DNA polymerases with 5-alkyl-2'-deoxyuridine 5'-triphosphates. Biochim Biophys Acta. 1980 Feb 29;606(2):196–201. doi: 10.1016/0005-2787(80)90029-5. [DOI] [PubMed] [Google Scholar]
  13. Sági J., Otvös L. Modified polynucleotides. IV. Template activity of 5-alkyluracil-containing poly [d(A-r5U)] copolymers for DNA and RNA polymerases. Nucleic Acids Res. 1979 Nov 24;7(6):1593–1601. doi: 10.1093/nar/7.6.1593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Sági J., Otvös L. Modified polynucleotides. V. Slow-down of nuclease action by 5-alkyluracil-containing DNAs. Biochem Biophys Res Commun. 1980 Jul 16;95(1):156–162. doi: 10.1016/0006-291x(80)90717-2. [DOI] [PubMed] [Google Scholar]
  15. Sági J., Szabolcs A., Szemzö A., Otvös L. (E)-5-(2-bromovinyl)-2'-deoxyuridine-5'-triphosphate as a DNA polymerase substrate. Nucleic Acids Res. 1981 Dec 21;9(24):6985–6994. doi: 10.1093/nar/9.24.6985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Veres Z., Szabolcs A., Szinai I., Dénes G., Jeney A. Enzymatic cleavage of 5-substituted-2'-deoxyuridines by pyrimidine nucleoside phosphorylases. Biochem Pharmacol. 1986 Mar 15;35(6):1057–1059. doi: 10.1016/0006-2952(86)90101-2. [DOI] [PubMed] [Google Scholar]

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

RESOURCES