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
. 1979 Jan;76(1):24–28. doi: 10.1073/pnas.76.1.24

Steroid diamine-nucleic acid interactions: partial insertion of dipyrandium between unstacked base pairs of the poly(dA-dT) duplex in solution.

D J Patel, L L Canuel
PMCID: PMC382868  PMID: 284337

Abstract

We report on an NMR investigation of steroid diamine.nucleic acid complexes as a function of phosphate-to-drug ratios in aqueous solution in order to evaluate the structural and kinetic aspects of the binding of a nonintercalative drug to a synthetic DNA in solution. The nonexchangeable proton chemical shift parameters for the dipyrandium.poly(dA-dT) complex demonstrate unstacking of base pairs and partial insertion of the steroid diamine at the complexation site. The chemical shifts and linewidths of the exchangeable protons as a function of pH demonstrate that the base pairs are intact but partially exposed to solvent at the steroid diamine binding site. The phosphorus chemical shifts suggest that the base pairs unstack upon complex formation without changes in the omega,omega' polynucleotide backbone torsion angles. The NMR line shape parameters require rapid exchange of the steroid diamine among potential binding sites and are consistent with greater segmental flexibility in the complex compared to the synthetic DNA in solution. The NMR experiments are discussed in relation to Sobell's proposed model [Sobell, H.M., Tsai, C.C., Gilbert, S.G., Jain, S.C. & Sakore, T.D. (1976) Proc. Natl. Acad. Sci USA 73, 3068-3072] for the steroid diamine-DNA complex.

Full text

PDF
25

Selected References

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

  1. Brunner W. C., Maestre M. F. Circular dichroism of films of polynucleotides. Biopolymers. 1974;13(2):345–357. doi: 10.1002/bip.1974.360130210. [DOI] [PubMed] [Google Scholar]
  2. Crick F. H., Klug A. Kinky helix. Nature. 1975 Jun 12;255(5509):530–533. doi: 10.1038/255530a0. [DOI] [PubMed] [Google Scholar]
  3. Crothers D. M., Hilbers C. W., Shulman R. G. Nuclear magnetic resonance study of hydrogen-bonded ring protons in Watson-Crick base pairs. Proc Natl Acad Sci U S A. 1973 Oct;70(10):2899–2901. doi: 10.1073/pnas.70.10.2899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gabbay E. J., Glaser R. Topography of nucleic acid helices in solutions. Proton magnetic resonance studies of the interaction specificities of steroidal amines with nucleic acid systems. Biochemistry. 1971 Apr 27;10(9):1665–1674. doi: 10.1021/bi00785a026. [DOI] [PubMed] [Google Scholar]
  5. Giessner-Prettre C., Pullman B., Borer P. N., Kan L. S., Ts'o P. O. Ring-current effects in the Nmr of nucleic acids: a graphical approach. Biopolymers. 1976 Nov;15(11):2277–2286. doi: 10.1002/bip.1976.360151114. [DOI] [PubMed] [Google Scholar]
  6. Gorenstein D. G., Findlay J. B., Momii R. K., Luxon B. A., Kar D. Temperature dependence of the 31P chemical shifts of nucleic acids. A prode of phosphate ester torsional conformations. Biochemistry. 1976 Aug 24;15(17):3796–3803. doi: 10.1021/bi00662a023. [DOI] [PubMed] [Google Scholar]
  7. Guéron M., Shulman R. G. 31P magnetic resonance of tRNA. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3482–3485. doi: 10.1073/pnas.72.9.3482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ivanov V. I., Minchenkova L. E., Minyat E. E., Frank-Kamenetskii M. D., Schyolkina A. K. The B to A transition of DNA in solution. J Mol Biol. 1974 Aug 25;87(4):817–833. doi: 10.1016/0022-2836(74)90086-2. [DOI] [PubMed] [Google Scholar]
  9. Kearns D. R., Patel D. J., Shulman R. G. High resolution nuclear magnetic resonance studies of hydrogen bonded protons of tRNA in water. Nature. 1971 Jan 29;229(5283):338–339. doi: 10.1038/229338a0. [DOI] [PubMed] [Google Scholar]
  10. Li H. J., Crothers D. M. Relaxation studies of the proflavine-DNA complex: the kinetics of an intercalation reaction. J Mol Biol. 1969 Feb 14;39(3):461–477. doi: 10.1016/0022-2836(69)90138-7. [DOI] [PubMed] [Google Scholar]
  11. Mahler H. R., Green G., Goutarel R., Khuong-Huu Q. Nucleic acid-small molecule interactions. VII. Further characterization of deoxyribonucleic acid-diamino steroid complexes. Biochemistry. 1968 Apr;7(4):1568–1582. doi: 10.1021/bi00844a046. [DOI] [PubMed] [Google Scholar]
  12. Patel D. J., Canuel L. L. Biphasic helix-coil transition of the ethidium bromide-poly (dA-dT) and the propidium diiodide - poly (dA-dT) complexes. Stabilization of base-pair regions centered about the intercalation site. Biopolymers. 1977 Apr;16(4):857–873. doi: 10.1002/bip.1977.360160410. [DOI] [PubMed] [Google Scholar]
  13. Patel D. J., Canuel L. L. Netropsin-poly(dA-dT) complex in solution: structure and dynamics of antibiotic-free base pair regions and those centered on bound netropsin. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5207–5211. doi: 10.1073/pnas.74.12.5207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Patel D. J., Canuel L. Nuclear magnetic resonance studies of the helix-coil transition of poly (dA-dT) in aqueous solution. Proc Natl Acad Sci U S A. 1976 Mar;73(3):674–678. doi: 10.1073/pnas.73.3.674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Patel D. J., Hilbers C. W. Proton nuclear magnetic resonance investigations of fraying in double-stranded d-ApTpGpCpApT in H2O solution. Biochemistry. 1975 Jun 17;14(12):2651–2656. doi: 10.1021/bi00683a014. [DOI] [PubMed] [Google Scholar]
  16. Patel D. J. Proton and phosphorus NMR studies of d-CpG(pCpG)n duplexes in solution. Helix-coil transition and complex formation with actinomycin-D. Biopolymers. 1976 Mar;15(3):533–558. doi: 10.1002/bip.1976.360150310. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Pohl F. M., Jovin T. M., Baehr W., Holbrook J. J. Ethidium bromide as a cooperative effector of a DNA structure. Proc Natl Acad Sci U S A. 1972 Dec;69(12):3805–3809. doi: 10.1073/pnas.69.12.3805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. SPATZ H., BALDWIN R. L. STUDY OF THE FOLDING OF THE DAT COPOLYMER BY KINETIC MEASUREMENTS OF MELTING. J Mol Biol. 1965 Feb;11:213–222. doi: 10.1016/s0022-2836(65)80052-3. [DOI] [PubMed] [Google Scholar]
  21. Saucier J. M. Physicochemical studies on the interaction of irehdiamine A with bihelical DNA. Biochemistry. 1977 Dec 27;16(26):5879–5889. doi: 10.1021/bi00645a036. [DOI] [PubMed] [Google Scholar]
  22. Sobell H. M., Reddy B. S., Bhandary K. K., Jain S. C., Sakore T. D., Seshadri T. P. Conformational flexibility in DNA structure as revealed by structural studies of drug intercalation and its broader implications in understanding the organization of DNA in chromatin. Cold Spring Harb Symp Quant Biol. 1978;42(Pt 1):87–102. doi: 10.1101/sqb.1978.042.01.010. [DOI] [PubMed] [Google Scholar]
  23. Sobell H. M., Tsai C. C., Gilbert S. G., Jain S. C., Sakore T. D. Organization of DNA in chromatin. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3068–3072. doi: 10.1073/pnas.73.9.3068. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sussman J. L., Trifonov E. N. Possibility of nonkinked packing of DNA in chromatin. Proc Natl Acad Sci U S A. 1978 Jan;75(1):103–107. doi: 10.1073/pnas.75.1.103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Waring M. Variation of the supercoils in closed circular DNA by binding of antibiotics and drugs: evidence for molecular models involving intercalation. J Mol Biol. 1970 Dec 14;54(2):247–279. doi: 10.1016/0022-2836(70)90429-8. [DOI] [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