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. 1982 Oct 11;10(19):6051–6066. doi: 10.1093/nar/10.19.6051

Modified polynucleotides. VI. Properties of a synthetic DNA containing the anti-herpes agent (E)-5-(2-bromovinyl)-2'-deoxyuridine.

J Sági, A Czuppon, M Kajtár, A Szabolcs, A Szemzö, L Otvös
PMCID: PMC320950  PMID: 6755397

Abstract

A new modified polydeoxynucleotide, a copolymer of nucleotides of 2'-deoxyadenosine and the very efficacious anti-herpesvirus agent (E)-5-(2-bromovinyl)-2'-deoxyuridine was synthesized with E. coli DNA polymerase I enzyme. It is characterized by its physical (absorption and circular dichroism spectra, thermal transition, sedimentation analysis) and bioorganic (template activity, stability) properties. Compared to poly [d(A-T)], the modified polydeoxynucleotide had a lower thermal stability but exhibited higher stability against DNases and higher template activity for DNA synthesis. Template activity for RNA synthesis of this template was, however, poor and extent of AMP and UMP incorporation was limited as well.

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Selected References

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  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. Allaudeen H. S., Kozarich J. W., Bertino J. R., De Clercq E. On the mechanism of selective inhibition of herpesvirus replication by (E)-5-(2-bromovinyl)-2'-deoxyuridine. Proc Natl Acad Sci U S A. 1981 May;78(5):2698–2702. doi: 10.1073/pnas.78.5.2698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chamberlin M. J. Comparative properties of DNA, RNA, and hybrid homopolymer pairs. Fed Proc. 1965 Nov-Dec;24(6):1446–1457. [PubMed] [Google Scholar]
  4. Cheng Y. C., Dutschman G., De Clercq E., Jones A. S., Rahim S. G., Verhelst G., Walker R. T. Differential affinities of 5-(2-halogenovinyl)-2'-deoxyuridines for deoxythymidine kinases of various origins. Mol Pharmacol. 1981 Jul;20(1):230–233. [PubMed] [Google Scholar]
  5. Dale R. M., Livingston D. C., Ward D. C. The synthesis and enzymatic polymerization of nucleotides containing mercury: potential tools for nucleic acid sequencing and structural analysis. Proc Natl Acad Sci U S A. 1973 Aug;70(8):2238–2242. doi: 10.1073/pnas.70.8.2238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dale R. M., Ward D. C. Mercurated polynucleotides: new probes for hybridization and selective polymer fractionation. Biochemistry. 1975 Jun 3;14(11):2458–2469. doi: 10.1021/bi00682a028. [DOI] [PubMed] [Google Scholar]
  7. De Clercq E., Descamps J., De Somer P., Barr P. J., Jones A. S., Walker R. T. (E)-5-(2-Bromovinyl)-2'-deoxyuridine: a potent and selective anti-herpes agent. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2947–2951. doi: 10.1073/pnas.76.6.2947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Greve J., Maestre M. F., Levin A. Circular dichroism of adenine and thymine containing synthetic polynucleotides. Biopolymers. 1977 Jul;16(7):1489–1504. doi: 10.1002/bip.1977.360160709. [DOI] [PubMed] [Google Scholar]
  9. Hansch C., Leo A., Unger S. H., Kim K. H., Nikaitani D., Lien E. J. "Aromatic" substituent constants for structure-activity correlations. J Med Chem. 1973 Nov;16(11):1207–1216. doi: 10.1021/jm00269a003. [DOI] [PubMed] [Google Scholar]
  10. Huang L. H., Farnet C. M., Ehrlich K. C., Ehrlich M. Digestion of highly modified bacteriophage DNA by restriction endonucleases. Nucleic Acids Res. 1982 Mar 11;10(5):1579–1591. doi: 10.1093/nar/10.5.1579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. INMAN R. B., BALDWIN R. L. HELIX--RANDOM COIL TRANSITIONS IN DNA HOMOPOLYMER PAIRS. J Mol Biol. 1964 Apr;8:452–469. doi: 10.1016/s0022-2836(64)80003-6. [DOI] [PubMed] [Google Scholar]
  12. Larsson A., Oberg B. Selective inhibition of herpesvirus deoxyribonucleic acid synthesis by acycloguanosine, 2'-fluoro-5-iodo-aracytosine, and (E)-5-(2-bromovinyl)-2'-deoxyuridine. Antimicrob Agents Chemother. 1981 May;19(5):927–929. doi: 10.1128/aac.19.5.927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lieberman M. W., Harvan D. J., Amacher D. E., Patterson J. B. Effect of mercuric and silver ions on cesium sulfate equilibrium buoyant densities of synthetic polydeoxyribonucleotides. Biochim Biophys Acta. 1976 Mar 17;425(3):265–277. doi: 10.1016/0005-2787(76)90253-7. [DOI] [PubMed] [Google Scholar]
  14. Maudgal P. C., De Clercq E., Descamps J., Missotten L., De Somer P., Busson R., Vanderhaeghe H., Verhelst G., Walker R. T., Jones A. S. (E)-5-(2-bromovinyl)-2'-Deoxyuridine in the treatment of experimental herpes simplex keratitis. Antimicrob Agents Chemother. 1980 Jan;17(1):8–12. doi: 10.1128/aac.17.1.8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Morgan A. R., Wells R. D. Specificity of the three-stranded complex formation between double-stranded DNA and single-stranded RNA containing repeating nucleotide sequences. J Mol Biol. 1968 Oct 14;37(1):63–80. doi: 10.1016/0022-2836(68)90073-9. [DOI] [PubMed] [Google Scholar]
  16. Pilet J., Blicharski J., Brahms J. Conformations and structural transitions in polydeoxynucleotides. Biochemistry. 1975 May 6;14(9):1869–1876. doi: 10.1021/bi00680a011. [DOI] [PubMed] [Google Scholar]
  17. Ruth J. L., Cheng Y. C. Nucleoside analogues with clinical potential in antivirus chemotherapy. The effect of several thymidine and 2'-deoxycytidine analogue 5'-triphosphates on purified human (alpha, beta) and herpes simplex virus (types 1, 2) DNA polymerases. Mol Pharmacol. 1981 Sep;20(2):415–422. [PubMed] [Google Scholar]
  18. SCHACHMAN H. K., ADLER J., RADDING C. M., LEHMAN I. R., KORNBERG A. Enzymatic synthesis of deoxyribonucleic acid. VII. Synthesis of a polymer of deoxyadenylate and deoxythymidylate. J Biol Chem. 1960 Nov;235:3242–3249. [PubMed] [Google Scholar]
  19. 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]
  20. 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]
  21. 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]
  22. 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]
  23. 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]
  24. Wells R. D., Larson J. E., Grant R. C., Shortle B. E., Cantor C. R. Physicochemical studies on polydeoxyribonucleotides containing defined repeating nucleotide sequences. J Mol Biol. 1970 Dec 28;54(3):465–497. doi: 10.1016/0022-2836(70)90121-x. [DOI] [PubMed] [Google Scholar]

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