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. 1978 Oct;75(10):4729–4733. doi: 10.1073/pnas.75.10.4729

Actinomycin D-deoxynucleotide interactions: binding isotherms at the benzenoid and quinoid portions of the drug.

H E Auer, T N Thompson
PMCID: PMC336193  PMID: 283386

Abstract

Titrations of actinomycin D (AMD) with dG and with dG-dC were monitored by circular dichroism at 380 nm and 470 nm. These wavelengths are sensitive predominantly to nucleotide binding processes at the benzenoid and quinoid portions, respectively, of the phenoxazone ring of the drug chromophore [Auer, H.E., Pawlowski-Konopnicki, B.E., Chiao, Y.C.C. & Krugh, T.R. (1978), Biopolymers, 17, 1891-1911.]. The temperature dependence of these isotherms was analyzed by the van't Hoff equation to obtain values for the enthalpy and entropy changes. For dG these are about -11 kcal mol-1 and -20 cal mol-1 deg-1, respectively, for complex formation at both the benzenoid and quinoid sites (1 cal = 4.184 J). The enthalpy and entropy changes for complex formation with dG-dC remain unchanged at the benzenoid site, but both values are more negative at the quinoid site. These results indicate that the additional process of binding C in the intercalated AMD-(dG-dC)2 complex, with respect to the simply stacked AMD-dG2 complex, has distinctive properties at the two sites, reflecting their structural differences. The ability to resolve binding processes at the two sites by circular dichroism has permitted us to suggest assignments for the two 31P magnetic resonance lines from the phosphodiester groups observed in the AMD-(pdG-dC)2 complex.

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Selected References

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  1. Arison B. H., Hoogsteen K. Nuclear magnetic resonance spectral studies on actinomycin D. Preliminary observations on the effect of complex formation with 5'-deoxyguanylic acid. Biochemistry. 1970 Sep 29;9(20):3976–3983. doi: 10.1021/bi00822a016. [DOI] [PubMed] [Google Scholar]
  2. Auer H. E., Pawloski-Konopnicki B. E., Krugh T. R. The absorption spectrum of actinomycin D. Evidence for three transitions in the visible band. FEBS Lett. 1977 Feb 1;73(2):167–170. doi: 10.1016/0014-5793(77)80973-3. [DOI] [PubMed] [Google Scholar]
  3. Behme M. T., Cordes E. H. Equilibrium constants for association of actinomycin D with several purine derivatives. Biochim Biophys Acta. 1965 Oct 11;108(2):312–313. doi: 10.1016/0005-2787(65)90017-1. [DOI] [PubMed] [Google Scholar]
  4. Cerami A., Reich E., Ward D. C., Goldberg I. H. The interaction of actinomycin with DNA: requirement for the 2-amino group of purines. Proc Natl Acad Sci U S A. 1967 Apr;57(4):1036–1042. doi: 10.1073/pnas.57.4.1036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Courtois Y., Guschlbauer W., Fromageot P. Interactions entre pigments et acides nucléiques. 6. Etude de l'interaction de l'actinomycine avec le DNA par dispersion optique rotatoire. Eur J Biochem. 1968 Oct 17;6(1):106–113. doi: 10.1111/j.1432-1033.1968.tb00426.x. [DOI] [PubMed] [Google Scholar]
  6. Crothers D. M., Sabol S. L., Ratner D. I., Müller W. Studies concerning the behavior of actinomycin in solution. Biochemistry. 1968 May;7(5):1817–1823. doi: 10.1021/bi00845a028. [DOI] [PubMed] [Google Scholar]
  7. Davanloo P., Crothers D. M. Kinetic studies of drug-dinucleotide complexes. Biochemistry. 1976 Nov 30;15(24):5299–5305. doi: 10.1021/bi00669a016. [DOI] [PubMed] [Google Scholar]
  8. Davanloo P., Crothers D. M. Phase partition studies of actinomycin-nucleotide complexes. Biochemistry. 1976 Oct 5;15(20):4433–4438. doi: 10.1021/bi00665a015. [DOI] [PubMed] [Google Scholar]
  9. GELLERT M., SMITH C. E., NEVILLE D., FELSENFELD G. ACTINOMYCIN BINDING TO DNA: MECHANISM AND SPECIFICITY. J Mol Biol. 1965 Mar;11:445–457. doi: 10.1016/s0022-2836(65)80001-8. [DOI] [PubMed] [Google Scholar]
  10. GOLDBERG I. H., RABINOWITZ M., REICH E. Basis of actinomycin action. I. DNA binding and inhibition of RNA-polymerase synthetic reactions by actinomycin. Proc Natl Acad Sci U S A. 1962 Dec 15;48:2094–2101. doi: 10.1073/pnas.48.12.2094. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Homer R. B. The circular dichroism of actinomycin D and its complexes with DNA and dGMP5'. Arch Biochem Biophys. 1969 Jan;129(1):405–407. doi: 10.1016/0003-9861(69)90193-3. [DOI] [PubMed] [Google Scholar]
  12. Jain S. C., Sobell H. M. Stereochemistry of actinomycin binding to DNA. I. Refinement and further structural details of the actinomycin-deoxyguanosine crystalline complex. J Mol Biol. 1972 Jul 14;68(1):1–20. doi: 10.1016/0022-2836(72)90258-6. [DOI] [PubMed] [Google Scholar]
  13. Krugh T. R. Association of actinomycin D and deoxyribodinucleotides as a model for binding of the drug to DNA. Proc Natl Acad Sci U S A. 1972 Jul;69(7):1911–1914. doi: 10.1073/pnas.69.7.1911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Krugh T. R., Chen Y. C. Actinomycin D-deoxynucleotide complexes as models for the actinomycin D-DNA complex. The use of nuclear magnetic resonance to determine the stoichiometry and the geometry of the complexes. Biochemistry. 1975 Nov 4;14(22):4912–4922. doi: 10.1021/bi00693a021. [DOI] [PubMed] [Google Scholar]
  15. Krugh T. R., Neely J. W. Actinomycin D-deoxydinucleotide interactions as a model for binding of the drug to deoxyribonucleic acid. Proton magnetic resonance results. Biochemistry. 1973 Oct 23;12(22):4418–4425. doi: 10.1021/bi00746a019. [DOI] [PubMed] [Google Scholar]
  16. Krugh T. R., Neely J. W. Actinomycin D-mononucleotide interactions as studied by proton magnetic resonance. Biochemistry. 1973 Apr 24;12(9):1775–1782. doi: 10.1021/bi00733a018. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Müller W., Spatz H. C. Uber die Struktur des Actinomycin-Desoxyguanosin-Komplexes. Z Naturforsch B. 1965 Sep;20(9):842–853. [PubMed] [Google Scholar]
  19. Patel D. J. NMR studies of the structure and stability of the 1 : 2 actinomycin D-d-pG-C complex in aqueous solution. Biochim Biophys Acta. 1976 Aug 2;442(1):98–108. doi: 10.1016/0005-2787(76)90180-5. [DOI] [PubMed] [Google Scholar]
  20. Patel D. J. Peptide antibiotic-dinucleotide interactions. Nuclear magnetic resonance investigations of complex formation between actinomycin D and d-pGpC in aqueous solution. Biochemistry. 1974 May 21;13(11):2388–2395. doi: 10.1021/bi00708a024. [DOI] [PubMed] [Google Scholar]
  21. Quadrifoglio F., Ciana A., Crescenzi V. Letter: On the interaction between actinomycin D and DNA. Biopolymers. 1976 Mar;15(3):595–597. doi: 10.1002/bip.1976.360150316. [DOI] [PubMed] [Google Scholar]
  22. Schara R., Müller W. Uber die Wechselwirkung des Actinomycin C 3 mit Mono- Di- und Oligonucleotiden. Eur J Biochem. 1972 Sep 18;29(2):210–216. doi: 10.1111/j.1432-1033.1972.tb01977.x. [DOI] [PubMed] [Google Scholar]
  23. Sobell H. M., Jain S. C. Stereochemistry of actinomycin binding to DNA. II. Detailed molecular model of actinomycin-DNA complex and its implications. J Mol Biol. 1972 Jul 14;68(1):21–34. doi: 10.1016/0022-2836(72)90259-8. [DOI] [PubMed] [Google Scholar]
  24. Wells R. D., Larson J. E. Studies on the binding of actinomycin D to DNA and DNA model polymers. J Mol Biol. 1970 Apr 28;49(2):319–342. doi: 10.1016/0022-2836(70)90248-2. [DOI] [PubMed] [Google Scholar]
  25. Yamaoka K., Ziffer H. The optical properties of actinomycin D. II. Optical activity of the deoxyribonucleic acid complex. Biochemistry. 1968 Mar;7(3):1001–1008. doi: 10.1021/bi00843a018. [DOI] [PubMed] [Google Scholar]
  26. Ziffer H., Yamaoka K., Mauger A. B. Optical properties of actinomycin D. I. Influence of the lactone rings on its optical activity. Biochemistry. 1968 Mar;7(3):996–1001. doi: 10.1021/bi00843a017. [DOI] [PubMed] [Google Scholar]

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