Skip to main content
NCBI home page
Nucleic Acids Research logoLink to Nucleic Acids Research
. 1983 Aug 25;11(16):5701–5715. doi: 10.1093/nar/11.16.5701

Calorimetric and spectroscopic investigation of drug--DNA interactions: II. Dipyrandium binding to poly d(AT).

L A Marky, J G Snyder, K J Breslauer
PMCID: PMC326308  PMID: 6889134

Abstract

We report the first calorimetric investigation of steroid diamine binding to a DNA duplex. Absorption spectroscopy, batch calorimetry, and differential scanning calorimetry (DSC) have been used to detect, monitor, and thermodynamically characterize the binding of the steroid diamine, dipyrandium, to poly d(AT). The following thermodynamic data for the binding in 16 mM Na+ at 25 degrees C have been obtained: delta G degree = -6.5 kcal/mol, delta H degree = +4.2 kcal/mol, and delta S = +36 e.u. We interpret the endothermic binding enthalpy in terms of steroid-induced conformational changes in the duplex (e.g. "kinking"). The large positive entropy is interpreted in terms of binding-induced release of bound water and condensed sodium ions. The salt-dependence of the binding constant is interpreted in terms of dipyrandium site-binding involving only one of the two charged ends of the steroid. The optical and DSC curves for the unsaturated steroid-poly d(AT) complexes exhibit biphasic behavior. A comparison of the van't Hoff and the calorimetric transition enthalpies reveals that steroid binding reduces the cooperativity of the transition.

Full text

PDF
5701

Selected References

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

  1. Breslauer K. J., Sturtevant J. M., Tinoco I., Jr Calorimetric and spectroscopic investigation of the helix-to-coil transition of a ribo-oligonucleotide: rA7U7. J Mol Biol. 1975 Dec 25;99(4):549–565. doi: 10.1016/s0022-2836(75)80171-9. [DOI] [PubMed] [Google Scholar]
  2. Crothers D. M. Calculation of binding isotherms for heterogenous polymers. Biopolymers. 1968 Apr;6(4):575–584. doi: 10.1002/bip.1968.360060411. [DOI] [PubMed] [Google Scholar]
  3. Dattagupta N., Hogan M., Crothers D. M. Does irehdiamine kink DNA? Proc Natl Acad Sci U S A. 1978 Sep;75(9):4286–4290. doi: 10.1073/pnas.75.9.4286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. 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]
  6. Gralla J., Crothers D. M. Free energy of imperfect nucleic acid helices. II. Small hairpin loops. J Mol Biol. 1973 Feb 5;73(4):497–511. doi: 10.1016/0022-2836(73)90096-x. [DOI] [PubMed] [Google Scholar]
  7. Jackson W. M., Brandts J. F. Thermodynamics of protein denaturation. A calorimetric study of the reversible denaturation of chymotrypsinogen and conclusions regarding the accuracy of the two-state approximation. Biochemistry. 1970 May 26;9(11):2294–2301. doi: 10.1021/bi00813a011. [DOI] [PubMed] [Google Scholar]
  8. MAHLER H. R., DUTTON G. NUCLEIC ACID INTERACTIONS. V. EFFECTS OF CYCLOBUXINE. J Mol Biol. 1964 Oct;10:157–175. doi: 10.1016/s0022-2836(64)80035-8. [DOI] [PubMed] [Google Scholar]
  9. Mahler H. R., Goutarel R., Khuong-Huu Q., Truong HO M. Nucleic acid interactions. VI. Effects of steroidal diamines. Biochemistry. 1966 Jul;5(7):2177–2191. doi: 10.1021/bi00871a005. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Manning G. S. Analysis of the ionic contribution to the affinity of steroid diamines for DNA. Biopolymers. 1979 Sep;18(9):2357–2358. doi: 10.1002/bip.1979.360180922. [DOI] [PubMed] [Google Scholar]
  12. Manning G. S. The molecular theory of polyelectrolyte solutions with applications to the electrostatic properties of polynucleotides. Q Rev Biophys. 1978 May;11(2):179–246. doi: 10.1017/s0033583500002031. [DOI] [PubMed] [Google Scholar]
  13. Marky L. A., Blumenfeld K. S., Breslauer K. J. Calorimetric and spectroscopic investigation of drug-DNA interactions. I. The binding of netropsin to poly d(AT). Nucleic Acids Res. 1983 May 11;11(9):2857–2870. doi: 10.1093/nar/11.9.2857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Marky L. A., Blumenfeld K. S., Kozlowski S., Breslauer K. J. Salt-dependent conformational transitions in the self-complementary deoxydodecanucleotide d(CGCAATTCGCG): evidence for hairpin formation. Biopolymers. 1983 Apr;22(4):1247–1257. doi: 10.1002/bip.360220416. [DOI] [PubMed] [Google Scholar]
  15. Marky L. A., Canuel L., Jones R. A., Breslauer K. J. Calorimetric and spectroscopic investigation of the helix-to-coil transition of the self-complementary deoxyribonucleotide ATGCAT. Biophys Chem. 1981 Apr;13(2):141–149. doi: 10.1016/0301-4622(81)80013-0. [DOI] [PubMed] [Google Scholar]
  16. Marky L. A., Patel D., Breslauer K. J. Effect of tetramethylammonium ion on the helix-to-coil transition of poly(deoxyadenylylthymidine): a nuclear magnetic resonance and calorimetric investigation. Biochemistry. 1981 Mar 17;20(6):1427–1431. doi: 10.1021/bi00509a004. [DOI] [PubMed] [Google Scholar]
  17. Mudd C., Berger R. L., Hopkins H. P., Friauf W. S., Gibson C. An optimized differential heat conduction solution microcalorimeter for thermal kinetic measurements. J Biochem Biophys Methods. 1982 Aug;6(3):179–203. doi: 10.1016/0165-022x(82)90042-2. [DOI] [PubMed] [Google Scholar]
  18. Patel D. J., Canuel L. L. Steroid diamine-nucleic acid interactions: partial insertion of dipyrandium between unstacked base pairs of the poly(dA-dT) duplex in solution. Proc Natl Acad Sci U S A. 1979 Jan;76(1):24–28. doi: 10.1073/pnas.76.1.24. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Record M. T., Jr, Anderson C. F., Lohman T. M. Thermodynamic analysis of ion effects on the binding and conformational equilibria of proteins and nucleic acids: the roles of ion association or release, screening, and ion effects on water activity. Q Rev Biophys. 1978 May;11(2):103–178. doi: 10.1017/s003358350000202x. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Scheffler I. E., Sturtevant J. M. Thermodynamics of the helix-coil transition of the alternating copolymer of deoxyadenylic acid and deoxythymidylic acid. J Mol Biol. 1969 Jun 28;42(3):577–580. doi: 10.1016/0022-2836(69)90244-7. [DOI] [PubMed] [Google Scholar]
  22. Sobell H. M., Tsai C. C., Jain S. C., Gilbert S. G. Visualization of drug-nucleic acid interactions at atomic resolution. III. Unifying structural concepts in understanding drug-DNA interactions and their broader implications in understanding protein-DNA interactions. J Mol Biol. 1977 Aug 15;114(3):333–365. doi: 10.1016/0022-2836(77)90254-6. [DOI] [PubMed] [Google Scholar]
  23. Waring M. J., Chisholm J. W. Uncoiling of bacteriophage PM2 DNA by binding of steroidal diamines. Biochim Biophys Acta. 1972 Feb 23;262(1):18–23. doi: 10.1016/0005-2787(72)90214-6. [DOI] [PubMed] [Google Scholar]
  24. Waring M. J., Henley S. M. Stereochemical aspects of the interaction between steroidal diamines and DNA. Nucleic Acids Res. 1975 Apr;2(4):567–586. doi: 10.1093/nar/2.4.567. [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 Nucleic Acids Research are provided here courtesy of Oxford University Press

RESOURCES