Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1986 Nov 25;14(22):9103–9115. doi: 10.1093/nar/14.22.9103

A theoretical study of anthracene and phenanthrene derivatives acting as A-T specific intercalators.

K X Chen, N Gresh, B Pullman
PMCID: PMC311932  PMID: 3786146

Abstract

Theoretical computations are performed on the comparative A-T versus G-C binding selectivities of two DNA intercalating molecules recently synthesized by Wilson et al. These are derivatives of phenanthrene and anthracene with side chains containing an hydroxy group bound to its C alpha carbon and a cationic amino group bound to its C beta carbon. We have optimized the binding energies of these phenanthrene and anthracene derivatives (1 and 2, respectively) to the double-stranded tetramers d(ATAT)2 and d(GCGC)2, the intercalation occurring in the central pyrimidine (3'-5') purine sequence. The sum of the intercalator-oligonucleotide intermolecular interaction energy plus the conformational energy variation of the intercalator upon binding were computed by the SIBFA procedures, which use empirical formulas based on ab initio SCF computations. Both compounds are found to bind more favourably to the AT sequence than to the GC one. Moreover, the affinity of 1 for the AT oligomer is computed to be larger than that of 2, whereas conversely that of 2 is larger than that of 1 for the GC oligomer. The AT versus GC binding selectivity of 1 is significantly larger than that of 2. These results are in excellent agreement with the experimental findings of Wilson et al. However, contrary to the suggestion of these authors the alpha-hydroxy group of the side chain of the intercalators does not seem to play a decisive role in determining the A-T specificity.

Full text

PDF
9103

Selected References

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

  1. Arnott S., Hukins D. W. Refinement of the structure of B-DNA and implications for the analysis of x-ray diffraction data from fibers of biopolymers. J Mol Biol. 1973 Dec 5;81(2):93–105. doi: 10.1016/0022-2836(73)90182-4. [DOI] [PubMed] [Google Scholar]
  2. Chen K. S., Gresh N., Pullman B. A theoretical investigation on the sequence selective binding of adriamycin to double-stranded polynucleotides. Nucleic Acids Res. 1986 Mar 11;14(5):2251–2267. doi: 10.1093/nar/14.5.2251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chen K. X., Gresh N., Pullman B. A theoretical investigation on the sequence selective binding of daunomycin to double-stranded polynucleotides. J Biomol Struct Dyn. 1985 Dec;3(3):445–466. doi: 10.1080/07391102.1985.10508434. [DOI] [PubMed] [Google Scholar]
  4. Chen K. X., Gresh N., Pullman B. A theoretical investigation on the sequence selective binding of mitoxantrone to double-stranded tetranucleotides. Nucleic Acids Res. 1986 May 12;14(9):3799–3812. doi: 10.1093/nar/14.9.3799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dasgupta D., Goldberg I. H. Mode of reversible binding of neocarzinostatin chromophore to DNA: base sequence dependency of binding. Nucleic Acids Res. 1986 Jan 24;14(2):1089–1105. doi: 10.1093/nar/14.2.1089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gresh N., Pullman B. A theoretical study of the nonintercalative binding of berenil and stilbamidine to double-stranded (dA-dT)n oligomers. Mol Pharmacol. 1984 May;25(3):452–458. [PubMed] [Google Scholar]
  7. Jones R. L., Lanier A. C., Keel R. A., Wilson W. D. The effect of ionic strength on DNA-ligand unwinding angles for acridine and quinoline derivatives. Nucleic Acids Res. 1980 Apr 11;8(7):1613–1624. doi: 10.1093/nar/8.7.1613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lown J. W., Morgan A. R., Yen S. F., Wang Y. H., Wilson W. D. Characteristics of the binding of the anticancer agents mitoxantrone and ametantrone and related structures to deoxyribonucleic acids. Biochemistry. 1985 Jul 16;24(15):4028–4035. doi: 10.1021/bi00336a034. [DOI] [PubMed] [Google Scholar]
  9. Miller K. J. Interactions of molecules with nucleic acids. I. An algorithm to generate nucleic acid structures with an application to the B-DNA structure and a counterclockwise helix. Biopolymers. 1979 Apr;18(4):959–980. doi: 10.1002/bip.1979.360180415. [DOI] [PubMed] [Google Scholar]
  10. Müller W., Crothers D. M. Studies of the binding of actinomycin and related compounds to DNA. J Mol Biol. 1968 Jul 28;35(2):251–290. doi: 10.1016/s0022-2836(68)80024-5. [DOI] [PubMed] [Google Scholar]
  11. Ornstein R. L., Rein R. Energetic and structural aspects of ethidium cation intercalation into DNA minihelices. Biopolymers. 1979 Nov;18(11):2821–2847. doi: 10.1002/bip.1979.360181112. [DOI] [PubMed] [Google Scholar]
  12. Ornstein R. L., Rein R. Energetics of intercalation specificity. I. Backbone unwinding. Biopolymers. 1979 May;18(5):1277–1291. doi: 10.1002/bip.1979.360180517. [DOI] [PubMed] [Google Scholar]
  13. Pack G. R., Loew G. Origins of the specificity in the intercalation of ethidium into nucleic acids. A theoretical analysis. Biochim Biophys Acta. 1978 Jun 22;519(1):163–172. doi: 10.1016/0005-2787(78)90070-9. [DOI] [PubMed] [Google Scholar]
  14. Pullman A., Pullman B. Molecular electrostatic potential of the nucleic acids. Q Rev Biophys. 1981 Aug;14(3):289–380. doi: 10.1017/s0033583500002341. [DOI] [PubMed] [Google Scholar]
  15. Sturm J., Schreiber L., Daune M. Binding of ligands to a one-dimensional heterogeneous lattice. II. Intercalation of tilorone with DNA and polynucleotides. Biopolymers. 1981 Apr;20(4):765–785. doi: 10.1002/bip.1981.360200410. [DOI] [PubMed] [Google Scholar]

Articles from Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES