Biopolym. Cell. 1999; 15(2):154-162.
http://dx.doi.org/10.7124/bc.000514
Structure and Function of Biopolymers
NMR analysis of the interaction of antibiotic daunomycin with deoxytetranucleotide, 5'-d(TpGpCpA), in aqueous solution
1Veselkov A. N., 2Eaton R. J., 1Baranovsky S. F., 1Osetrov S. G., 1Pahomov V. I., 1Bolotin P. A., 1Djimant L. N., 2Davies D. B.
  1. Sevastopol National Technical University
    33, Universytetska Str., Sevastopol, Ukraine, 99053
  2. Birkbeck, University of London
    Malet Str., Bloomsbury, London WC1E 7HX, UK

Abstract

One-dimentional and two-dimentional (2D-TOCSY and 2D-NCJESY) homonuclear H NMR spectroscopy and heteronuclear 2D- 1H-31P-NMR spectroscopy have been used to investigate the comple-xation of the antibiotic daunomycin with deoxytetranucleotide 5'-d(TpGpCpA) in aqueous salt solution. The equilibrium reaction constants, relative content of different types of complexes as a function of concentration and temperature of solution and thermo-dynamical parameters ΔH and ΔS of complexation of the molecules have been calculated using experimental concentrational and temperature dependences of the proton chemical shifts of the interacting molecules. Analysis of the results has shown that the most favourable binding sites for daunomycin are triplet nucleotidc sequences. Binding of the second daunomycin molecule with both single-stranded and duplex forms of the tetranucleotide is highly anticooperative. The most favourable structure of 1:2 antibiotic-deoxy-tetranudeotide complex has been constructed using the calculated limiting proton chemical shifts of daunomycin protons in the' intercalated complex and 2D-NOE data.
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References

[1] Arcamone F. Doxorubicin: anticancer antibiotics. New York: Acad, press, 1981. 325 p.
[2] Arcamone F, Penco S. Antracyclines and Antracenedione—based Anticancer Agents. Ed. JW. Lown. New York: Elsevier, 1988:1—43.
[3] Pigram WJ, Fuller W, Hamilton LD. Stereochemistry of intercalation: interaction of daunomycin with DNA. Nat New Biol. 1972;235(53):17-9.
[4] Quigley GJ, Wang AH, Ughetto G, van der Marel G, van Boom JH, Rich A. Molecular structure of an anticancer drug-DNA complex: daunomycin plus d(CpGpTpApCpG). Proc Natl Acad Sci U S A. 1980;77(12):7204-8.
[5] Wang AH, Ughetto G, Quigley GJ, Rich A. Interactions between an anthracycline antibiotic and DNA: molecular structure of daunomycin complexed to d(CpGpTpApCpG) at 1.2-A resolution. Biochemistry. 1987;26(4):1152-63.
[6] Dalgleish DG, Fey G, Kersten W. Circular dichroism studies of complexes of the antibiotics daunomycin, nogalamycin, chromomycin, and mithramycin with DNA. Biopolymers. 1974;13(9):1757-66.
[7] Neidle S, Sanderson MR. Molecular Aspects of Anti-Cancer Drug Action. Eds S. Neidle, MJ Waring. Weinlan: Verlag Chemie, 1983:35—57.
[8] Chaires JB. Equilibrium studies on the interaction of daunomycin with deoxypolynucleotides. Biochemistry. 1983;22(18):4204-11.
[9] Newlin DD, Miller KJ, Pilch DF. Interactions of molecules with nucleic acids. VII. Intercalation and T.A specificity of daunomycin in DNA. Biopolymers. 1984;23(1):139-58.
[10] Chen KX, Gresh N, Pullman B. A theoretical investigation on the sequence selective binding of daunomycin to double-stranded polynucleotides. J Biomol Struct Dyn. 1985;3(3):445-66.
[11] Chaires JB, Dattagupta N, Crothers DM. Studies on interaction of anthracycline antibiotics and deoxyribonucleic acid: equilibrium binding studies on interaction of daunomycin with deoxyribonucleic acid. Biochemistry. 1982;21(17):3933-40.
[12] Chaires JB, Fox KR, Herrera JE, Britt M, Waring MJ. Site and sequence specificity of the daunomycin-DNA interaction. Biochemistry. 1987;26(25):8227-36.
[13] Davies DB, Djimant LN, Veselkov AN. 1H NMR Structural Analysis of the Interactions of Proflavine with Self-Complementary Deoxytetranucleosides of Different Base Sequence. Nucleosides Nucleotides 1994. 13(1-3):637—655.
[14] Davies DB, Karawajew L, Veselkov AN. 1H-NMR structural analysis of ethidium bromide complexation with self-complementary deoxytetranucleotides 5'-d(ApCpGpT), 5'-d(ApGpCpT), and 5'-d(TpGpCpA) in aqueous solution. Biopolymers. 1996;38(6):745-57.
[15] Huang YM, Phillips DR. Thermodynamics of the interaction of daunomycin with DNA. Biophys Chem. 1977;6(3):363-8.
[16] Veselkov A. N., Djimant L. N., Bolotin P. A., Baranovsky S. F., Veselkov D. A., Shipp D., Davies D. B. Investigation of the interaction of ethidium bromide with self complementary deoxytetranucleotide 5'-d (ApCpGpT) in aqueous solution by the method of 1H NMR spectroscopy Biopolym. Cell. 1995; 11(3-4):42-54
[17] Evans JNS. Biomolecular NMR spectroscopy. London: Oxf. Univ. press, 1995. 444 p.
[18] Eaton PJ, Veselkov DA, Davies DB, Dymant LH, Veselkov AN. Investigation of self-association of anthracycline antibiotic daunomycin in aqueous solution by 1H NMR spectroscopy. Khim fizika.1999. 18, N 6
[19] Veselkov AN, Dymant LN, Kodintsev VV, Lisiutin VA, Parkes H, Davies D. Self-association of deoxytetraribonucleoside triphosphates d(TpGpCpA) in an aqueous solution by 1H NMR spectroscopy. Biofizika. 1995;40(2):283-92.
[20] Searle MS, Lane AN. 31P NMR investigation of the backbone conformation and dynamics of the hexamer duplex d(5'-GCATGC)2 in its complex with the antibiotic nogalamycin. FEBS Lett. 1992;297(3):292-6.
[21] Veselkov AN, Moroshkina EB, Soboleva OI, Frisman EV. Comparative study of DNA interactions with daunomycin and proflavine in a solution. Mol Biol (Mosk). 1984;18(2):481-7.
[22] Davies DB, Djimant LN, Baranovsky SF, Veselkov AN. 1H-NMR determination of the thermodynamics of drug complexation with single-stranded and double-stranded oligonucleotides in solution: ethidium bromide complexation with the deoxytetranucleotides 5'-d(ApCpGpT), 5'-d(ApGpCpT), and 5'-d(TpGpCpA). Biopolymers. 1997;42(3):285-95.
[23] Chaires JB. Thermodynamics of the daunomycin-DNA interaction: ionic strength dependence of the enthalpy and entropy. Biopolymers. 1985;24(2):403-19.
[24] Ross PD, Subramanian S. Thermodynamics of protein association reactions: forces contributing to stability. Biochemistry. 1981;20(11):3096-102.
[25] Marky LA, Blumenfeld KS, Breslauer KJ. Calorimetric and spectroscopic investigation of drug-DNA interactions. I. The binding of netropsin to poly d(AT). Nucleic Acids Res. 1983;11(9):2857-70.
[26] Sturtevant JM. Heat capacity and entropy changes in processes involving proteins. Proc Natl Acad Sci USA. 1977;74(6):2236-40.
[27] Kennard O, Hunter WN. Oligonucleotide structure: a decade of results from single crystal X-ray diffraction studies. Q Rev Biophys. 1989;22(3):327-79.
[28] Remeta DP, Mudd CP, Berger RL, Breslauer KJ. Thermodynamic characterization of daunomycin-DNA interactions: microcalorimetric measurements of daunomycin-DNA binding enthalpies. Biochemistry. 1991;30(40):9799-809.
[29] Giessner-Prettre C, Pullman B. Quantum mechanical calculations of NMR chemical shifts in nucleic acids. Q Rev Biophys. 1987;20(3-4):113-72.
[30] Poltev VI, Teplukhin AV. Conformational implications of some nucleotide sequences. Int J Quant Chem. 1989. 35(1):91-102.
[31] Dickerson RE. Definitions and nomenclature of nucleic acid structure parameters. J Biomol Struct Dyn. 1989;6(4):627-34.
[32] Neidle S, Taylor G. Nucleic acid binding drugs. Part IV. The crystal structure of the anti-cancer agent daunomycin. Biochim Biophys Acta. 1977;479(4):450-9.
[33] Searle MS. NMR Studies of Drug—DNA interactions. Prog Nucl Magn Reson Spectrosc. 1993; 25(5):403—480.
[34] Blackburn GM, Gait JM. Nucleic Acids in Chemistry and Biology. Oxford; New York; Tokyo: Oxford Univ. press,1990. 336 p.