Skip to main content

Isohelical DNA-Binding Oligomers: Antiviral Activity and Application for the Design of Nanostructured Devices

  • Conference paper
Nanomaterials for Application in Medicine and Biology

Abstract

We performed a systematic search for new structural motifs isohelical to double-stranded DNA and found five motifs that can be used for the design and synthesis of new DNA-binding oligomers. Some of the DNA-binding oligomers can be equipped with fluorescence chromophores and metal-chelating groups and may serve as conductive wires in nano-scaled electric circuits. A series of new DNA-binding ligands were synthesized by a modular assembly of pyrrole carboxamides and novel pseudopeptides of the form (XY)n. Here, Y is a glycine residue; n is the degree of polymerization. X is an unusual amino acid residue containing a five-membered aromatic ring. Antiviral activity of bis-linked netropsin derivatives is studied. Bis-netropsins containing 15 and 31 lysine residues at the N-termini inhibit most effectively reproduction of the herpes virus type 1 in the Vero cell culture, including virus variants resistant to acyclovir and its analogues. Antiviral activity of bis-linked netropsin derivatives is correlated with their ability to interact with long clusters of AT-base pairs in the origin of replication of the viral DNA.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. C. Bailly and J. B. Chaires, Sequence-specific DNA minor groove binders. Design and synthesis of netropsin and distamycin analogues, Bioconjug. Chem. 9(5), 513–538 (1998).

    Article  PubMed  CAS  Google Scholar 

  2. M. L. Kopka, C. Yoon, D. Goodsell, P. Pjura, and R. E. Dickerson, The molecular origin of DNA-drug specificity in netropsin and distamycin, Proc. Natl. Acad. Sci. USA. 82(5), 1376–1380 (1985).

    Article  PubMed  ADS  CAS  Google Scholar 

  3. M. Coll, C. A. Frederick, A. H. Wang, and A. Rich, A bifurcated hydrogen bonded conformation in the d(AT) base pairs of the DNA dodecamer d(CGCAAATTTGCG) and its complex with distamycin, Proc. Natl. Acad. Sci. USA. 84(23), 8385–8389 (1987).

    Article  PubMed  ADS  CAS  Google Scholar 

  4. R. E. Dickerson, Helix structures and molecular recognition by B-DNA, in: Oxford Handbook of Nucleic Acid Structure, S. Neidle (ed.) (Oxford University Press, New York, 2001), pp. 145–197.

    Google Scholar 

  5. R. E. Klevit, D. E. Wemmer, and B. R. Reid, 1H NMR studies on the interaction between distamycin A and a symmetrical DNA dodecamer, Biochemistry 25(11), 3296–3303 (1986).

    Article  PubMed  CAS  Google Scholar 

  6. A. A. Khorlin, A. S. Krylov, S. L. Grokhovsky, A. L. Zhuze, A. S. Zasedatelev, G. V. Gursky, and B. P. Gottikh, A new type of AT-specific ligand constructed of two netropsin-like molecules, FEBS Lett. 118(2), 311–314 (1980).

    Article  PubMed  CAS  Google Scholar 

  7. G. V. Gursky, A. S. Zasedatelev, A. L. Zhuze, A. A. Khorlin, S. L. Grokhovsky, S. A. Streltsov, A. N. Surovaya, A. M. Nikitin, A. S. Krylov, V. O. Retchinsky, R. S. Beabealashvili, and B. P. Gottikh, Synthetic sequence-specific ligands, Cold Spring Harbor Symp. Quant. Biol. 47, 367–378 (1983).

    PubMed  Google Scholar 

  8. J. W. Lown, K. Krowicki, U. G. Bhat, A. Skorobogaty, B. Ward, and J. C. Dabrowiak, Molecular recognition between oligopeptides and nucleic acids–novel imidazole-containing oligopeptides related to netropsin that exhibit altered DNA-sequence specificity, Biochemistry 25(23), 7408–7416 (1986).

    Article  PubMed  CAS  Google Scholar 

  9. J. W. Lown, K. Krowicki, J. Balzarini, R. A. Newman, and E. De Clerk, Novel linked antiviral and antitumor agents related to netropsin and distamycin: synthesis and biological evaluation, J. Med. Chem. 32(10), 2368–2375 (1989).

    Article  PubMed  CAS  Google Scholar 

  10. J. G. Pelton and D. E. Wemmer, Structural characterization of a 2:1 distamycin A d(CGCAAATTGGC) complex by two-dimensional NMR, Proc. Natl. Acad. Sci. 86(15), 5723–5727 (1989).

    Article  PubMed  ADS  CAS  Google Scholar 

  11. M. Mrksich, M. E. Parks, and P. B. Dervan, Hairpin peptide motif, A new class of oligopeptides for sequence-specific recognition in the minor groove of double-helical DNA, J. Am. Chem. Soc. 116, 7983–7988 (1994).

    Article  CAS  Google Scholar 

  12. X. Chen, B. Ramakrishnan, S. T. Rao, and M. Sundaralingam, Binding of two distamycin A molecules in the minor groove of an alternating B-DNA duplex, Struct. Biol. 1, 169–175 (1994).

    Article  CAS  Google Scholar 

  13. V. A. Nikolaev, S. L. Grokhovsky, A. N. Surovaya, T. A. Leinsoo, N. Yu. Sidorov, A. S. Zasedatelev, A. L. Zhuze, G. A. Strachan, R. H. Shafer, and G. V. Gursky, Design of sequence-specific DNA binding ligands that use a two-stranded peptide motif for DNA sequence recognition, J. Biomol. Struct. Dyn. 14(1), 31–47 (1996).

    PubMed  CAS  Google Scholar 

  14. B. H. Geierstanger, M. Mrksich, P. B. Dervan, and D. E. Wemmer, Design of a G7C-specific DNA minor groove-binding peptide, Science 266, 646–650 (1994).

    Article  ADS  Google Scholar 

  15. M. L. Kopka, D. S. Goodsell, G. W. Han, T. K. Chiu, J. W. Lown, and R. E. Dickerson, Defining GC-specificity in the minor groove: side-by-side binding of diimidazole lexitropsin to CATGGCCATG, Structure 5, 1033–1044 (1997).

    Article  PubMed  CAS  Google Scholar 

  16. A. N. Surovaya, G. Burckhardt, S. L. Grokhovsky, E. Birch-Hirschfeld, G. V. Gursky, and C. Zimmer, Hairpin polyamides that use parallel and antiparallel side-by-side peptide motifs in binding to DNA, J. Biomol. Struct. Dyn. 14(5), 595–606 (1997).

    PubMed  CAS  Google Scholar 

  17. S. L. Grokhovsky, A. N. Surovaya, G. Burckhardt, V. F. Pismensky, B. K. Chernov, C. Zimmer, and G. V. Gursky, DNA sequence recognition by bis-linked netropsin and distamycin derivatives, FEBS Lett. 439(3), 346–350 (1998).

    Article  PubMed  CAS  Google Scholar 

  18. A. N. Surovaya, G. Burckhardt, S. L. Grokhovsky, E. Birch-Hirschfeld, A. M. Nikitin, H. Fritzsche, C. Zimmer, and G. V. Gursky, Binding of bis-linked netropsin derivatives in the parallel-stranded hairpin form to DNA. J. Biomol. Struct. Dyn. 18(5), 689–701, (2001).

    PubMed  CAS  Google Scholar 

  19. T. A. Beerman, J. M. Woynarowski, R. D. Sigmund, L. S. Gawron, K. E. Rao, and J. W. Lown, Netropsin and bis-netropsin analogs as inhibitors of the catalytic activity of mammalian DNA topoisomerase II and topoisomerase cleavable complexes, Biochim. Biophys. Acta. 1090(1), 52–60 (1991).

    PubMed  CAS  Google Scholar 

  20. G. Burkhardt, H. Simon, K. Storl, H. Triebel, A. Walter, J. W. Lown, and C. Zimmer, DNA binding studies and influence on the activity of DNA topoisomerases of bis-netropsins: different effects of analogs containing cis and trans ethylene linkers, J. Biomol. Struct. Dyn. 15(1), 81–95 (1997).

    Google Scholar 

  21. M. E. Filipowsky, M. L. Kopka, M. Brazil-Zison, J. W. Lown, and R. E. Dickerson, Linked lexitropsins and the in vitro inhibition of HIV-1 reverse transcriptase RNA-directed DNA polymerization: a novel induced-fit of 3, 5 m-pyridyl bisdistamycin to enzyme-associated template-primer, Biochemistry 35(48), 15397–15410 (1996).

    Article  PubMed  CAS  Google Scholar 

  22. N. Neamati, A. Mazumder, S. Sunder, J. M. Owen, M. Tandon, J. W. Lown, and Y. Pommier, Highly potent synthetic polyamides, bis-distamycins, and lexitropsins as inhibitors of human immunodeficiency virus type 1 integrase, Mol. Pharmacol. 54(2), 280–290 (1998).

    PubMed  CAS  Google Scholar 

  23. S. White, J. W. Szewczyk, J. M. Turner, E. E. Baird, and P. B. Dervan, Recognition of the four Watson-Crick base pairs in the DNA minor groove by synthetic ligands, Nature 391(6666), 468–471 (1998).

    Article  PubMed  ADS  CAS  Google Scholar 

  24. A. R. Urbach, J. W. Szewczyk, S. White, J. M. Turner, E. E. Baird, and P. B. Dervan, Sequence selectivity of 3-hydroxypyrrole/pyrrole ring pairings in the DNA minor groove, J. Am. Chem. Soc. 121(50), 11621–11629 (1999).

    Article  CAS  Google Scholar 

  25. L. A. Dickinson, R. J. Gulizia, J. W. Trauger, E. E. Baird, D. E. Mosier, J. M. Gottesfeld, and P. B. Dervan, Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands, Proc. Natl. Acad. Sci. USA. 95(22), 12890–12895 (1998).

    Article  PubMed  ADS  CAS  Google Scholar 

  26. S. L. Belikov, S. L. Grokhovsky, M. G. Isaguliants, A. N. Surovaya, and G. V. Gursky, Sequence-specific minor groove binding ligands as potential regulators of gene expression in Xenopus Laevis oocytes, J. Biomol. Struct. Dyn. 23(2), 193–202 (2005).

    PubMed  CAS  Google Scholar 

  27. A. S. Zasedatelev, Geometrical correlations useful for design of sequence-specific DNA narrow groove binding ligands, FEBS Lett. 281(1–2), 209–211 (1991).

    Article  PubMed  CAS  Google Scholar 

  28. D. Goodsell and R. E. Dickerson, Isohelical analysis of DNA groove-binding drugs, J. Med. Chem. 29(5), 727–733 (1986).

    Article  PubMed  CAS  Google Scholar 

  29. A. M. Nikitin and G. V. Gursky, New structural motifs isohelical to DNA, Doklady Biochem. Biophys. 390(1–6), 139–142 (2003).

    Article  CAS  Google Scholar 

  30. M. S. Molchanova, W. Shcherbukhin, and N. S. Zefirov, Computer generation of molecular structures by SMOG program, J. Chem. Inform. Comp. Sci. 36(4), 888–899 (1996).

    CAS  Google Scholar 

  31. T. A. Halgren, Merck molecular force field: I. Basis, form, scope, parameterization and performance of MMFF94, J. Comput. Chem. 17(5–6), 490–519 (1996).

    Article  CAS  Google Scholar 

  32. J. P. Michael and G. Pattenden, Marin metabolites and metal ion chelation: the facts and the fantasies, Angew. Chem., Int. Ed. 32(1), 1–23 (1993).

    Article  Google Scholar 

  33. P. Yorgey, J. Lee, J. Kördel, E. Vivas, P. Warner, D. Jebarathan, and R. Kolter, Posttranslational modifications in microcin B17 define an additional class of DNA gyrase inhibitors. Proc. Natl. Acad. Sci. USA. 91, 4517–4523 (1994).

    Article  ADS  Google Scholar 

  34. C. L. Kielkopf, R. E. Bremer, S. White, J. W. Szewczyk, J. M. Turner, E. E. Baird, P. B. Dervan, and D. C. Rees, Structural effects of DNA sequence on T7A recognition by hydroxypyrrole/pyrrole pairs in the minor groove, J. Mol. Biol., 295(3), 557–567 (2000).

    Article  PubMed  CAS  Google Scholar 

  35. A. M. Nikitin, S. A. Rodin, V. F. Pismensky, A. N. Surovaya, and G. V. Gursky, A new pseudopeptide motif for designing specific DNA-binding compounds capable of recognizing long DNA sequences, Doklady Biochem. Biophys. 384(1–6), 167–171 (2002).

    Article  CAS  Google Scholar 

  36. C. K. Chiang, C. R. Fincher Jr., Y. W. Park, A. G. Heeger, H. Shirakawa, E. J. Louis, S. C. Gau, and A. G. MacDiarmid, Electrical conductivity in doped polyacetylene, Phys. Rev. Lett. 39(17), 1098–1101 (1977).

    Article  ADS  CAS  Google Scholar 

  37. T. Hasegawa, S. Haraguchi, M. Numata, C. Li, A.-H. Bae, T. Fujisawa, K. Kaneko, K. Sakurai, and S. Shinkai, Poly(diacetylene)-nanofibers can be fabricated through photo-irradiation using natural polysaccharide schizophyllan as a one-dimensional mold, Org. Biomol. Chem. 3(24), 4321–4328 (2005).

    Article  PubMed  CAS  Google Scholar 

  38. M. Shimomura, R. Mitamura, J. Matsumoto, and K. Ijiro, DNA-mimetics: towards novel molecular devices having molecular information, Synthetic Metals 133–134, 473–479 (2003).

    Article  CAS  Google Scholar 

  39. N. C. Seeman, Structural DNA nanotechnology: an overview, Methods Mol. Biol. 303, 143–166 (2005).

    PubMed  CAS  Google Scholar 

  40. E. Braun, Y. Eichen, U. Sivan, and G. Ben-Yoseph, DNA-templated assembly and electrode attachment of a conducting silver wire, Nature. 391(6669), 775–778 (1998).

    Article  PubMed  ADS  CAS  Google Scholar 

  41. V. L. Andronova, S. L. Grokhovsky, S. L. Surovaya, and Gursky, G. A. Galegov, Antiherpetic activity of dimeric derivatives of netropsin, Doklady Biochem. Biophys. 380(1–6), 345–348 (2001).

    Article  CAS  Google Scholar 

  42. A. N. Surovaya, S. L. Grokhovsky, V. L. Andronova, G. A. Galegov, and G. V. Gursky, DNA binding properties and antiviral activity of two bis-netropsins containing cis-diammineplatinum(II) group in the linker between two netropsin moeties, Book of the abstract: Albany 2007, Conservation 15, June 19–23 2007.

    Google Scholar 

  43. A. N. Surovaya, V. L. Andronova, S. L. Grokhovsky, G. A. Galegov, and G. V. Gursky, DNA-binding and antiviral activity of bis-netropsins, Biophysics 50(6), 884–893 (2005).

    Google Scholar 

  44. A. Aslani, M. Olsson, and P. Ellias, ATP-dependent unwinding of a minimal origin of DNA replication by the origin-binding protein and single-stranded DNA binding protein ICP8 from herpes simplex virus type I, J. Biol. Chem. 227, 41204–41212 (2002).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Science + Business Media B.V

About this paper

Cite this paper

Gursky, G., Nikitin, A., Surovaya, A., Grokhovsky, S., Andronova, V., Galegov, G. (2008). Isohelical DNA-Binding Oligomers: Antiviral Activity and Application for the Design of Nanostructured Devices. In: Giersig, M., Khomutov, G.B. (eds) Nanomaterials for Application in Medicine and Biology. NATO Science for Peace and Security Series. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6829-4_2

Download citation

Publish with us

Policies and ethics