Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1990 Jul 15;269(2):329–334. doi: 10.1042/bj2690329

Effects of variation in the structure of spermine on the association with DNA and the induction of DNA conformational changes.

H S Basu 1, H C Schwietert 1, B G Feuerstein 1, L J Marton 1
PMCID: PMC1131580  PMID: 2386479

Abstract

The effects of spermine and spermine analogues on the B-Z transition of poly(dG-me5dC) and on the aggregation and 'melting' temperature of calf thymus DNA were studied by spectroscopic methods. The association constants of these polyamines with double- and single-stranded calf thymus DNA were calculated from their effects on the melting temperature. The effect of these compounds on the release of ethidium bromide (EB) from an EB-DNA complex were measured by a spectrofluorimetric method. This efficiency of the polyamine-induced B-Z transition strongly depended on the length of the central carbon chains of the compounds and on the functional groups attached to the carbon chains. Both the terminal primary amino groups and the length of the central carbon chain affected the aggregation of DNA. The affinity of the analogues for DNA increased as the number of n-butyl groups increased, but decreased with either an increase or a decrease in the length of the central carbon chain. The effect of spermine and spermine analogues on the release of EB from an EB-DNA complex did not always correlate with the affinities of analogues for calf thymus DNA. In particular, tetra-amines with more than one n-butyl group bound better to DNA than did spermine, but released bound EB and induced aggregation of DNA less well than did spermine. We postulate that either a bend and/or other localized conformational changes of DNA are responsible for the spermine-induced aggregation of DNA and the release of EB from the EB-DNA complex.

Full text

PDF
329

Selected References

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

  1. Baillon J. G., Mamont P. S., Wagner J., Gerhart F., Lux P. Fluorinated analogues of spermidine as substrates of spermine synthase. Eur J Biochem. 1988 Sep 15;176(2):237–242. doi: 10.1111/j.1432-1033.1988.tb14274.x. [DOI] [PubMed] [Google Scholar]
  2. Basu H. S., Feuerstein B. G., Deen D. F., Lubich W. P., Bergeron R. J., Samejima K., Marton L. J. Correlation between the effects of polyamine analogues on DNA conformation and cell growth. Cancer Res. 1989 Oct 15;49(20):5591–5597. [PubMed] [Google Scholar]
  3. Basu H. S., Feuerstein B. G., Zarling D. A., Shafer R. H., Marton L. J. Recognition of Z-RNA and Z-DNA determinants by polyamines in solution: experimental and theoretical studies. J Biomol Struct Dyn. 1988 Oct;6(2):299–309. doi: 10.1080/07391102.1988.10507714. [DOI] [PubMed] [Google Scholar]
  4. Basu H. S., Marton L. J. The interaction of spermine and pentamines with DNA. Biochem J. 1987 May 15;244(1):243–246. doi: 10.1042/bj2440243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Basu H. S., Shafer R. H., Marton L. J. A stopped-flow H-D exchange kinetic study of spermine-polynucleotide interactions. Nucleic Acids Res. 1987 Jul 24;15(14):5873–5886. doi: 10.1093/nar/15.14.5873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Becker M., Misselwitz R., Damaschun H., Damaschun G., Zirwer D. Spermine-DNA complexes build up metastable structures. Small-angle X-ray scattering and circular dichroism studies. Nucleic Acids Res. 1979 Nov 10;7(5):1297–1309. doi: 10.1093/nar/7.5.1297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Berman H. M., Young P. R. The interaction of intercalating drugs with nucleic acids. Annu Rev Biophys Bioeng. 1981;10:87–114. doi: 10.1146/annurev.bb.10.060181.000511. [DOI] [PubMed] [Google Scholar]
  9. Braunlin W. H., Strick T. J., Record M. T., Jr Equilibrium dialysis studies of polyamine binding to DNA. Biopolymers. 1982 Jul;21(7):1301–1314. doi: 10.1002/bip.360210704. [DOI] [PubMed] [Google Scholar]
  10. Bresloff J. L., Crothers D. M. DNA-ethidium reaction kinetics: demonstration of direct ligand transfer between DNA binding sites. J Mol Biol. 1975 Jun 15;95(1):103–123. doi: 10.1016/0022-2836(75)90339-3. [DOI] [PubMed] [Google Scholar]
  11. Bresloff J. L., Crothers D. M. Equilibrium studies of ethidium--polynucleotide interactions. Biochemistry. 1981 Jun 9;20(12):3547–3553. doi: 10.1021/bi00515a038. [DOI] [PubMed] [Google Scholar]
  12. Cain B. F., Baguley B. C., Denny W. A. Potenial antitumor agents. 28. Deoxyribonucleic acid polyintercalating agents. J Med Chem. 1978 Jul;21(7):658–668. doi: 10.1021/jm00205a013. [DOI] [PubMed] [Google Scholar]
  13. Feuerstein B. G., Pattabiraman N., Marton L. J. Spermine-DNA interactions: a theoretical study. Proc Natl Acad Sci U S A. 1986 Aug;83(16):5948–5952. doi: 10.1073/pnas.83.16.5948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gosule L. C., Schellman J. A. DNA condensation with polyamines I. Spectroscopic studies. J Mol Biol. 1978 May 25;121(3):311–326. doi: 10.1016/0022-2836(78)90366-2. [DOI] [PubMed] [Google Scholar]
  15. Jain S. C., Sobell H. M. Visualization of drug-nucleic acid interactions at atomic resolution. VII. Structure of an ethidium/dinucleoside monophosphate crystalline complex, ethidium: uridylyl(3'-5') adenosine. J Biomol Struct Dyn. 1984 Mar;1(5):1161–1177. doi: 10.1080/07391102.1984.10507510. [DOI] [PubMed] [Google Scholar]
  16. Jain S. C., Sobell H. M. Visualization of drug-nucleic acid interactions at atomic resolution. VIII. Structures of two ethidium/dinucleoside monophosphate crystalline complexes containing ethidium: cytidylyl(3'-5') guanosine. J Biomol Struct Dyn. 1984 Mar;1(5):1179–1194. doi: 10.1080/07391102.1984.10507511. [DOI] [PubMed] [Google Scholar]
  17. Jain S. C., Tsai C. C., Sobell H. M. Visualization of drug-nucleic acid interactions at atomic resolution. II. Structure of an ethidium/dinucleoside monophosphate crystalline complex, ethidium:5-iodocytidylyl (3'-5') guanosine. J Mol Biol. 1977 Aug 15;114(3):317–331. doi: 10.1016/0022-2836(77)90253-4. [DOI] [PubMed] [Google Scholar]
  18. Lamos M. L., Walker G. T., Krugh T. R., Turner D. H. Fluorescence-detected circular dichroism of ethidium bound to poly(dG-dC) and poly(dG-m5dC) under B- and Z-form conditions. Biochemistry. 1986 Feb 11;25(3):687–691. doi: 10.1021/bi00351a027. [DOI] [PubMed] [Google Scholar]
  19. LePecq J. B., Paoletti C. A fluorescent complex between ethidium bromide and nucleic acids. Physical-chemical characterization. J Mol Biol. 1967 Jul 14;27(1):87–106. doi: 10.1016/0022-2836(67)90353-1. [DOI] [PubMed] [Google Scholar]
  20. Marquet R., Wyart A., Houssier C. Influence of DNA length on spermine-induced condensation. Importance of the bending and stiffening of DNA. Biochim Biophys Acta. 1987 Aug 25;909(3):165–172. doi: 10.1016/0167-4781(87)90074-1. [DOI] [PubMed] [Google Scholar]
  21. Neidle S., Abraham Z. Structural and sequence-dependent aspects of drug intercalation into nucleic acids. CRC Crit Rev Biochem. 1984;17(1):73–121. doi: 10.3109/10409238409110270. [DOI] [PubMed] [Google Scholar]
  22. Pegg A. E. Polyamine metabolism and its importance in neoplastic growth and a target for chemotherapy. Cancer Res. 1988 Feb 15;48(4):759–774. [PubMed] [Google Scholar]
  23. 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]
  24. Pörschke D., Jung M. Stability decrease of RNA double helices by phenylalanine-, tyrosine- and tryptophane-amides. Analysis in terms of site binding and relation to melting proteins. Nucleic Acids Res. 1982 Oct 11;10(19):6163–6176. doi: 10.1093/nar/10.19.6163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Stewart K. D. The effect of structural changes in a polyamine backbone on its DNA-binding properties. Biochem Biophys Res Commun. 1988 May 16;152(3):1441–1446. doi: 10.1016/s0006-291x(88)80447-9. [DOI] [PubMed] [Google Scholar]
  26. Tabor C. W., Tabor H. Polyamines. Annu Rev Biochem. 1984;53:749–790. doi: 10.1146/annurev.bi.53.070184.003533. [DOI] [PubMed] [Google Scholar]
  27. Thomas T. J., Messner R. P. Structural specificity of polyamines in left-handed Z-DNA formation. Immunological and spectroscopic studies. J Mol Biol. 1988 May 20;201(2):463–467. doi: 10.1016/0022-2836(88)90155-6. [DOI] [PubMed] [Google Scholar]
  28. Tsai C. C., Jain S. C., Sobell H. M. Visualization of drug-nucleic acid interactions at atomic resolution. I. Structure of an ethidium/dinucleoside monophosphate crystalline complex, ethidium:5-iodouridylyl (3'-5') adenosine. J Mol Biol. 1977 Aug 15;114(3):301–315. doi: 10.1016/0022-2836(77)90252-2. [DOI] [PubMed] [Google Scholar]
  29. Vertino P. M., Bergeron R. J., Cavanaugh P. F., Jr, Porter C. W. Structural determinants of spermidine-DNA interactions. Biopolymers. 1987 May;26(5):691–703. doi: 10.1002/bip.360260510. [DOI] [PubMed] [Google Scholar]
  30. Walker G. T., Stone M. P., Krugh T. R. Ethidium binding to left-handed (Z) DNAs results in regions of right-handed DNA at the intercalation site. Biochemistry. 1985 Dec 3;24(25):7462–7471. doi: 10.1021/bi00346a065. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES