Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1986 Mar;83(6):1617–1621. doi: 10.1073/pnas.83.6.1617

B- to Z-DNA transition probed by oligonucleotides containing methylphosphonates.

L Callahan, F S Han, W Watt, D Duchamp, F J Kézdy, K Agarwal
PMCID: PMC323134  PMID: 3456606

Abstract

The simulation of the B--Z-DNA transition by using space-filling models of the dimer d(C-G) shows the possibility of hydrogen-bond formation between the N-2 amino group of the partially rotated guanine and one of the 5'-phosphate oxygens of deoxyguanylic acid. To probe the importance of this postulated interaction, analogs of the hexamer d(C-G)3 were synthesized. These analogs contained a methylphosphonate linkage, of distinct stereochemistry, which replaced the first 5'-phosphate linkage of deoxyguanosine. The CD spectra in high salt concentration showed that the hexamer containing a methylphosphonate linkage with the RP stereochemistry formed Z-DNA to the same extent as d(C-G)3, whereas the hexamer containing a methylphosphonate linkage with the SP stereochemistry did not form Z-DNA. These results are consistent with a mechanism in which an interaction between the N-2 amino group of guanine and the prochiral SP oxygen of deoxyguanosine 5'-phosphate kinetically controls the formation of Z-DNA. A water bridge between the N-2 amino group of guanine and the 3'-phosphate oxygen of deoxyguanylic acid has been implicated in the stabilization of Z-DNA. To probe the importance of this water bridge, two additional analogs of the hexamer d(C-G)3 were synthesized. These analogs contained a methylphosphonate linkage, of distinct stereochemistry, that replaced the first deoxyguanosine 3'-phosphate. The CD spectra showed that the hexamer containing a methylphosphonate linkage of the RP stereochemistry underwent the transition to Z-DNA to the same extent as d(C-G)3, whereas the hexamer containing a methylphosphonate linkage of the SP stereochemistry underwent the transition to Z-DNA to a 35% lesser extent. Thus the water bridge involving the prochiral SP oxygen provides modest stabilization energy for Z-DNA. These studies, therefore, suggest that the B--Z-DNA transition is regulated both thermodynamically and kinetically through hydrogen-bond interactions involving phosphate oxygens and the N-2 amino group of guanine.

Full text

PDF
1617

Images in this article

1618Image
on p.1618
1618Image
on p.1618
1618Image
on p.1618

Selected References

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

  1. Agarwal K. L., Riftina F. Synthesis and enzymatic properties of deoxyribooligonucleotides containing methyl and phenylphosphonate linkages. Nucleic Acids Res. 1979 Jul 11;6(9):3009–3024. doi: 10.1093/nar/6.9.3009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Behe M., Felsenfeld G. Effects of methylation on a synthetic polynucleotide: the B--Z transition in poly(dG-m5dC).poly(dG-m5dC). Proc Natl Acad Sci U S A. 1981 Mar;78(3):1619–1623. doi: 10.1073/pnas.78.3.1619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Dickerson R. E., Drew H. R., Conner B. N., Wing R. M., Fratini A. V., Kopka M. L. The anatomy of A-, B-, and Z-DNA. Science. 1982 Apr 30;216(4545):475–485. doi: 10.1126/science.7071593. [DOI] [PubMed] [Google Scholar]
  4. Efimov V. A., Reverdatto S. V., Chakhmakhcheva O. G. New effective method for the synthesis of oligonucleotides via phosphotriester intermediates. Nucleic Acids Res. 1982 Nov 11;10(21):6675–6694. doi: 10.1093/nar/10.21.6675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gaffney B. L., Marky L. A., Jones R. A. The influence of the purine 2-amino group on DNA conformation and stability. Synthesis and conformational analysis of d[T(2-aminoA)]3. Nucleic Acids Res. 1982 Jul 24;10(14):4351–4361. doi: 10.1093/nar/10.14.4351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Harvey S. C. DNA structural dynamics: longitudinal breathing as a possible mechanism for the B in equilibrium Z transition. Nucleic Acids Res. 1983 Jul 25;11(14):4867–4878. doi: 10.1093/nar/11.14.4867. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Holak T. A., Borer P. N., Levy G. C., van Boom J. H., Wang A. H. 31P-NMR analysis of the B to Z transition in double-stranded (dC-dG)3 and (dC-dG)4 in high salt solution. Nucleic Acids Res. 1984 Jun 11;12(11):4625–4635. doi: 10.1093/nar/12.11.4625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jovin T. M., van de Sande J. H., Zarling D. A., Arndt-Jovin D. J., Eckstein F., Füldner H. H., Greider C., Grieger I., Hamori E., Kalisch B. Generation of left-handed Z-DNA in solution and visualization in polytene chromosomes by immunofluorescence. Cold Spring Harb Symp Quant Biol. 1983;47(Pt 1):143–154. doi: 10.1101/sqb.1983.047.01.019. [DOI] [PubMed] [Google Scholar]
  9. Kang D. S., Harvey S. C., Wells R. D. Diepoxybutane forms a monoadduct with B-form (dG-dC)n.(dG-dC)n and a crosslinked diadduct with the left-handed Z-form. Nucleic Acids Res. 1985 Aug 12;13(15):5645–5656. doi: 10.1093/nar/13.15.5645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kuzmich S., Marky L. A., Jones R. A. Specifically alkylated DNA fragments. Synthesis and physical characterization of d[CGC(O6Me)GCG] and d[CGT(O6Me)GCG]. Nucleic Acids Res. 1983 May 25;11(10):3393–3403. doi: 10.1093/nar/11.10.3393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Miller P. S., Agris C. H., Murakami A., Reddy P. M., Spitz S. A., Ts'o P. O. Preparation of oligodeoxyribonucleoside methylphosphonates on a polystyrene support. Nucleic Acids Res. 1983 Sep 24;11(18):6225–6242. doi: 10.1093/nar/11.18.6225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Miller P. S., Yano J., Yano E., Carroll C., Jayaraman K., Ts'o P. O. Nonionic nucleic acid analogues. Synthesis and characterization of dideoxyribonucleoside methylphosphonates. Biochemistry. 1979 Nov 13;18(23):5134–5143. doi: 10.1021/bi00590a017. [DOI] [PubMed] [Google Scholar]
  13. Olson W. K., Srinivasan A. R., Marky N. L., Balaji V. N. Theoretical probes of DNA conformation examining the B leads to Z conformational transition. Cold Spring Harb Symp Quant Biol. 1983;47(Pt 1):229–241. doi: 10.1101/sqb.1983.047.01.028. [DOI] [PubMed] [Google Scholar]
  14. Pohl F. M., Jovin T. M. Salt-induced co-operative conformational change of a synthetic DNA: equilibrium and kinetic studies with poly (dG-dC). J Mol Biol. 1972 Jun 28;67(3):375–396. doi: 10.1016/0022-2836(72)90457-3. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Sarma M. H., Gupta G., Dhingra M. M., Sarma R. H. During B-Z transition there is no large scale breakage of Watson-Crick base pairs. A direct demonstration using 500 MHz 1H NMR spectroscopy. J Biomol Struct Dyn. 1983 Oct;1(1):59–81. doi: 10.1080/07391102.1983.10507426. [DOI] [PubMed] [Google Scholar]
  17. Vorlíckovă M., Kypr J., Stokrová S., Sponar J. A Z-like form of poly(dA-dC).poly(dG-dT) in solution? Nucleic Acids Res. 1982 Feb 11;10(3):1071–1080. doi: 10.1093/nar/10.3.1071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Wang A. H., Quigley G. J., Kolpak F. J., Crawford J. L., van Boom J. H., van der Marel G., Rich A. Molecular structure of a left-handed double helical DNA fragment at atomic resolution. Nature. 1979 Dec 13;282(5740):680–686. doi: 10.1038/282680a0. [DOI] [PubMed] [Google Scholar]
  19. Wing R., Drew H., Takano T., Broka C., Tanaka S., Itakura K., Dickerson R. E. Crystal structure analysis of a complete turn of B-DNA. Nature. 1980 Oct 23;287(5784):755–758. doi: 10.1038/287755a0. [DOI] [PubMed] [Google Scholar]
  20. van de Sande J. H., Jovin T. M. Z* DNA, the left-handed helical form of poly[d(G-C)] in MgCl2-ethanol, is biologically active. EMBO J. 1982;1(1):115–120. doi: 10.1002/j.1460-2075.1982.tb01133.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES