Theoretical and Experimental Characterization of Polyamine/DNA Interactions

  • Burt G. Feuerstein
  • Hirak S. Basu
  • Laurence J. Marton
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 250)


For several years, work in our laboratory has been directed toward an understanding of the interactions of polyamines and nucleic acids. The initial impetus to this research was the finding that the cytotoxicity of antineoplastic agents such as cis-platinum and the 2-chloroethylnitrosoureas are altered in tumor cells in which intracellular levels of polyamines had been depleted by pretreatment with α-difluoromethylornithine (1, 2). It is thought that these agents kill cells by forming DNA interstrand crosslinks that prevent replication and lead to cell death. One possible explanation for the effects of polyamine depletion on cytotoxicity is that the conformation of intracellular DNA is altered, which would affect the mechanism of crosslink formation.


Minor Groove Major Groove Phosphate Backbone Amino Proton Helical Axis 
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  1. 1.
    D.T. Hung, D.F. Deen, J. Seidenfeld, and L.J. Marton, Sensitization of 9L rat brain gliosarcoma cells to l,3-bis (2-chloroethyD-1-nitrosourea by ot-difluoromethylomithine, an ornithine decarboxylase inhibitor. Cancer Res., 41: 2783 (1981).PubMedGoogle Scholar
  2. 2.
    S. M. Oredsson, D.F. Deen, and L.J. Marton, Decreased cytotoxicity of cis-diamminedichloroplatinum (II) by α-difluoromethylornithine depletion of polyamines in 9L rat brain tumor cells in vitro. Cancer Res., 42: 1296 (1982).PubMedGoogle Scholar
  3. 3.
    L.C. Gosule and J. A. Schellman, DNA condensation with polyamines. J. Mol. Biol., 121: 311, 327 (1978).PubMedCrossRefGoogle Scholar
  4. 4.
    R. Marquet, C. Houssier, and E. Fredericq, An electro-optical study of the mechanisms of DNA condensation induced by spermine, Biochem. Biophys. ACTA, 825: 365 (1985).PubMedGoogle Scholar
  5. 5.
    M. Behe and G. Felsenfeld, Effects of methylation on a synthetic polynucleotide: the B-Z transition in poly(dG-5medC). Proc. Natl. Acad. Sci. U.S.A., 78: 1619 (1981).PubMedCrossRefGoogle Scholar
  6. 6.
    B.G. Feuerstein and L.J. Marton, Specificity and binding in polyamine/nucleic acid interactions, in: “The Physiology of Polyamines, ” U. Bachrach and Y. Heimer, eds, CRC Press, Boca Raton (in press).Google Scholar
  7. 7.
    U.C. Singh, P.K. Weiner, J. Caldwell, and P.A. Kollman, Program AMBER UCSF, Version 3.0, Univesity of California, 1986.Google Scholar
  8. 8.
    B.G. Feuerstein, N. Pattabiraman, and L.J. Marton, Spermine DNA interactions: A theoretical study. Proc. Natl. Acad. Sci. U.S.A., 83: 5948 (1986).PubMedCrossRefGoogle Scholar
  9. 9.
    A.M. Liquori, L. Constantino, V. Crescenzi, V. Elia, E. Giglio, R. Puliti, M. DeSantis-Savino, and V. Vitigliano, Complexes between DNA and polyamines: A molecular model. J. Mol. Biol., 24: 113 (1967).CrossRefGoogle Scholar
  10. 10.
    M. Tsuboi, On the melting temperature of nucleic acids in solution, Bull. Chem. Soc. Jpn., 37: 1514 (1964).CrossRefGoogle Scholar
  11. 11.
    B.G. Feuerstein, N. Pattabiraman, and L.J. Marton, Molecular mechanics of the interactions of spermine with DNA (submitted).Google Scholar
  12. 12.
    B.G. Feuerstein, N. Pattabiraman, and L.J. Marton, Molecular dynamics of spermine binding to DNA (submitted).Google Scholar
  13. 13.
    E.E. Minyat, V.I. Ivasnov, A.M. Kritzyn, L.E. Minchenkova, and A.K. Schyolkina, Spermine and spermidine-induced B to A transition of DNA in solution. J. Mol. Biol., 128: 397(1978).CrossRefGoogle Scholar
  14. 14.
    W.C. Earnshaw and S.R. Casjens, DNA packaging by the double stranded DNA bacteriophages, Cell, 21: 319 (1980).PubMedCrossRefGoogle Scholar
  15. 15.
    K.A. Marx and G.C. Ruben, A study of ΦX-174 DNA torus and lambda DNA torus tertiary structure and the implications for DNA self assembly, J. Biol. Struct. Dynam., 4: 23–39 (1986).CrossRefGoogle Scholar
  16. 16.
    H.S. Basu, R.H. Shafer, and L.J. Marton, A stopped-flow H-D exchange kinetics study of spermine-polynucleotide interactions, Nuc. Acid Res., 15: 5873 (1987).CrossRefGoogle Scholar
  17. 17.
    A. Rich, A. Nordheim, and A.-H. Wang, The chemistry and biology of left-handed 2-DNA, Ann. Rev. Biochem., 53: 791 (1984).PubMedCrossRefGoogle Scholar
  18. 18.
    H.S. Basu, B.G. Feuerstein, D.A. Zarling, R.S. Shafer, and L.J. Marton, Recognition of Z-RNA and Z-DNA determinants by polyamines in solution: experimental and theoretical studies, J. Biomol. Struct. Dyn. (in press).Google Scholar
  19. 19.
    G.J. Quigley, The interactions of ions, water, and drugs with DNA, in: “Molecular Structure and Biological Activity,” J.F. Griffith and W.L. Duax, eds., Elsevier Biomédical Press, Amsterdam, 1982, p. 317.Google Scholar
  20. 20.
    P.M. Vertino, R.J. Bergeron, P.F. Cavanaugh, and C.W. Porter, Structural determinants of spermidine/DNA interactions, Biopolymers, 26: 691 (1987).PubMedCrossRefGoogle Scholar
  21. 21.
    T.J. Thomas and R.P. Messner, Structural specificity of polyamines in left-handed Z-DNA formation, J. Mol. Biol., 201: 463 (1988).PubMedCrossRefGoogle Scholar
  22. 22.
    H.S. Basu and L.J. Marton, The interaction of spermine and pentamines with DNA, Biochem. J., 244: 243 (1987)PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Burt G. Feuerstein
    • 1
  • Hirak S. Basu
    • 1
  • Laurence J. Marton
    • 1
  1. 1.Department of Laboratory Medicine and the Brain Tumor Research Center of the Department of Neurological Surgery, School of MedicineUniversity of CaliforniaSan FranciscoUSA

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