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. 1996 Dec 1;24(23):4660–4667. doi: 10.1093/nar/24.23.4660

Watson-Crick base-pairing properties of bicyclo-DNA.

M Bolli 1, H U Trafelet 1, C Leumann 1
PMCID: PMC146318  PMID: 8972851

Abstract

A series of sequences of the DNA analog bicyclo-DNA, 6-12 nucleotides in length and containing all four natural nucleobases, were prepared and their Watson-Crick pairing properties with complementary RNA and DNA, as well as in its own series, were analyzed by UV-melting curves and CD-spectroscopy. The results can be summarized as follows: bicyclo-DNA forms stable Watson-Crick duplexes with complementary RNA and DNA, the duplexes with RNA generally being more stable than those with DNA. Pyrimidine-rich bicyclo-DNA sequences form duplexes of equal or slightly increased stability with DNA or RNA, whereas purine-rich sequences show decreased affinity to complementary DNA and RNA when compared with wild-type (DNA-DNA, DNA-RNA) duplexes. In its own system, bicyclo-DNA prefers antiparallel strand alignment and strongly discriminates for base mismatches. Duplexes are always inferior in stability compared with the natural ones. A detailed analysis of the thermodynamic properties was performed with the sequence 5'-GGATGGGAG-3'x 5'-CTCCCATCC-3' in both backbone systems. Comparison of the pairing enthalpy and entropy terms shows an enthalpic advantage for DNA association (delta deltaH = -18 kcal x (mol)-1)) and an entropic advantage for bicyclo-DNA association (delta deltaS = 49 cal x K(-1) x mol(-1), leading to a delta deltaG 25 degrees C of -3.4 kcal x mol(-1) in favor of the natural duplex. The salt dependence of Tm for this sequence is more pronounced in the case of bicyclo-DNA due to increased counter ion screening from the solvent. Furthermore bicyclo-DNA sequences are more stable towards snake venom phosphodiesterase by a factor of 10-20, and show increased stability in fetal calf serum by a factor of 8 compared with DNA.

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Selected References

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  1. Bolli M., Litten J. C., Schütz R., Leumann C. J. Bicyclo-DNA: a Hoogsteen-selective pairing system. Chem Biol. 1996 Mar;3(3):197–206. doi: 10.1016/s1074-5521(96)90263-x. [DOI] [PubMed] [Google Scholar]
  2. Cazenave C., Chevrier M., Nguyen T. T., Hélène C. Rate of degradation of [alpha]- and [beta]-oligodeoxynucleotides in Xenopus oocytes. Implications for anti-messenger strategies. Nucleic Acids Res. 1987 Dec 23;15(24):10507–10521. doi: 10.1093/nar/15.24.10507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Drew H. R., Wing R. M., Takano T., Broka C., Tanaka S., Itakura K., Dickerson R. E. Structure of a B-DNA dodecamer: conformation and dynamics. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2179–2183. doi: 10.1073/pnas.78.4.2179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Durland R. H., Kessler D. J., Gunnell S., Duvic M., Pettitt B. M., Hogan M. E. Binding of triple helix forming oligonucleotides to sites in gene promoters. Biochemistry. 1991 Sep 24;30(38):9246–9255. doi: 10.1021/bi00102a017. [DOI] [PubMed] [Google Scholar]
  5. Eder P. S., DeVine R. J., Dagle J. M., Walder J. A. Substrate specificity and kinetics of degradation of antisense oligonucleotides by a 3' exonuclease in plasma. Antisense Res Dev. 1991 Summer;1(2):141–151. doi: 10.1089/ard.1991.1.141. [DOI] [PubMed] [Google Scholar]
  6. Fairall L., Martin S., Rhodes D. The DNA binding site of the Xenopus transcription factor IIIA has a non-B-form structure. EMBO J. 1989 Jun;8(6):1809–1817. doi: 10.1002/j.1460-2075.1989.tb03575.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hare D. R., Wemmer D. E., Chou S. H., Drobny G., Reid B. R. Assignment of the non-exchangeable proton resonances of d(C-G-C-G-A-A-T-T-C-G-C-G) using two-dimensional nuclear magnetic resonance methods. J Mol Biol. 1983 Dec 15;171(3):319–336. doi: 10.1016/0022-2836(83)90096-7. [DOI] [PubMed] [Google Scholar]
  8. Hoke G. D., Draper K., Freier S. M., Gonzalez C., Driver V. B., Zounes M. C., Ecker D. J. Effects of phosphorothioate capping on antisense oligonucleotide stability, hybridization and antiviral efficacy versus herpes simplex virus infection. Nucleic Acids Res. 1991 Oct 25;19(20):5743–5748. doi: 10.1093/nar/19.20.5743. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kang C., Zhang X., Ratliff R., Moyzis R., Rich A. Crystal structure of four-stranded Oxytricha telomeric DNA. Nature. 1992 Mar 12;356(6365):126–131. doi: 10.1038/356126a0. [DOI] [PubMed] [Google Scholar]
  10. Laughlan G., Murchie A. I., Norman D. G., Moore M. H., Moody P. C., Lilley D. M., Luisi B. The high-resolution crystal structure of a parallel-stranded guanine tetraplex. Science. 1994 Jul 22;265(5171):520–524. doi: 10.1126/science.8036494. [DOI] [PubMed] [Google Scholar]
  11. Liu K., Miles H. T., Frazier J., Sasisekharan V. A novel DNA duplex. A parallel-stranded DNA helix with Hoogsteen base pairing. Biochemistry. 1993 Nov 9;32(44):11802–11809. doi: 10.1021/bi00095a008. [DOI] [PubMed] [Google Scholar]
  12. Manning G. S. The molecular theory of polyelectrolyte solutions with applications to the electrostatic properties of polynucleotides. Q Rev Biophys. 1978 May;11(2):179–246. doi: 10.1017/s0033583500002031. [DOI] [PubMed] [Google Scholar]
  13. Marky L. A., Blumenfeld K. S., Kozlowski S., Breslauer K. J. Salt-dependent conformational transitions in the self-complementary deoxydodecanucleotide d(CGCAATTCGCG): evidence for hairpin formation. Biopolymers. 1983 Apr;22(4):1247–1257. doi: 10.1002/bip.360220416. [DOI] [PubMed] [Google Scholar]
  14. Marky L. A., Breslauer K. J. Calculating thermodynamic data for transitions of any molecularity from equilibrium melting curves. Biopolymers. 1987 Sep;26(9):1601–1620. doi: 10.1002/bip.360260911. [DOI] [PubMed] [Google Scholar]
  15. McCall M., Brown T., Hunter W. N., Kennard O. The crystal structure of d(GGATGGGAG): an essential part of the binding site for transcription factor IIIA. Nature. 1986 Aug 14;322(6080):661–664. doi: 10.1038/322661a0. [DOI] [PubMed] [Google Scholar]
  16. Milligan J. F., Matteucci M. D., Martin J. C. Current concepts in antisense drug design. J Med Chem. 1993 Jul 9;36(14):1923–1937. doi: 10.1021/jm00066a001. [DOI] [PubMed] [Google Scholar]
  17. Morvan F., Rayner B., Imbach J. L., Thenet S., Bertrand J. R., Paoletti J., Malvy C., Paoletti C. alpha-DNA II. Synthesis of unnatural alpha-anomeric oligodeoxyribonucleotides containing the four usual bases and study of their substrate activities for nucleases. Nucleic Acids Res. 1987 Apr 24;15(8):3421–3437. doi: 10.1093/nar/15.8.3421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pieles U., Zürcher W., Schär M., Moser H. E. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry: a powerful tool for the mass and sequence analysis of natural and modified oligonucleotides. Nucleic Acids Res. 1993 Jul 11;21(14):3191–3196. doi: 10.1093/nar/21.14.3191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Record M. T., Jr, Anderson C. F., Lohman T. M. Thermodynamic analysis of ion effects on the binding and conformational equilibria of proteins and nucleic acids: the roles of ion association or release, screening, and ion effects on water activity. Q Rev Biophys. 1978 May;11(2):103–178. doi: 10.1017/s003358350000202x. [DOI] [PubMed] [Google Scholar]
  20. Smith F. W., Feigon J. Quadruplex structure of Oxytricha telomeric DNA oligonucleotides. Nature. 1992 Mar 12;356(6365):164–168. doi: 10.1038/356164a0. [DOI] [PubMed] [Google Scholar]
  21. Sproat B. S., Lamond A. I., Beijer B., Neuner P., Ryder U. Highly efficient chemical synthesis of 2'-O-methyloligoribonucleotides and tetrabiotinylated derivatives; novel probes that are resistant to degradation by RNA or DNA specific nucleases. Nucleic Acids Res. 1989 May 11;17(9):3373–3386. doi: 10.1093/nar/17.9.3373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sun J. S., De Bizemont T., Duval-Valentin G., Montenay-Garestier T., Hélène C. Extension of the range of recognition sequences for triple helix formation by oligonucleotides containing guanines and thymines. C R Acad Sci III. 1991;313(13):585–590. [PubMed] [Google Scholar]
  23. Wagner R. W. Gene inhibition using antisense oligodeoxynucleotides. Nature. 1994 Nov 24;372(6504):333–335. doi: 10.1038/372333a0. [DOI] [PubMed] [Google Scholar]

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