Biopolym. Cell. 1998; 14(2):117-126.
Structure and Function of Biopolymers
1H-NMR investigation of coraplexation of acridine dye proflavine with deoxytetraribonucleoside triphosphate 5'-d(TpGpCpA) in aqueous solution
1Eaton R. A., 1Veselkov D. A., 2Djimant L. N., 2Baranovsky S. F., 2Osetrov S. G., 1Davies D. B., 2Veselkov A. N.
  1. Birkbeck, University of London
    Malet Str., Bloomsbury, London WC1E 7HX, UK
  2. Sevastopol National Technical University
    33, Universytetska Str., Sevastopol, Ukraine, 99053

Abstract

The interaction of acridine dye proflavine with self-complementary deoxytetraribonucleoside triphosphate 5'-d(TpGpCpA) in aqueous salt solution has been studied by one- and two- dimentional 500 MHz 1H-NMR spectroscopy. Concentration and temperature dependences of proton chemical shifts of the interacting molecules have been measured. Different schemes of complexation of proflavine with the tetranucleotide have been analysed and the equilibrium constants, enthalpies ΔH, entropies ΔS of different reactions leading to the formation of 1:1, 1:2, 2:1, 2:2 complexes have been determined. The specific features of the dynamic equilibrium of different complexes as a function of the drug-tetranucleotide ratio have been examined. It is concluded that proflavine intercalates preferentially to pyrimidine-purine TG- and CA-sites of the tetranucleotide sequence. Comparative analysis of the distinctive features of the intercalative binding of proflavine and that of phenan-tridinium dye ethidium bromide studied earlier has shown that intensity of selective interaction of aromatic ligands with pyrimidine-purine sequence depends on the base content and type of the bases flanking the binding sites. The most favourable structures 1:2 and 2:2 proflavine-tetranucleotide complexes have been constructed using calculated values of induced chemical shift of dye protons and 2D-NOE spectra.

References

[1] Gale EE, Cundliffe E, Reynolds PE et al. The molecular basis of antibiotic action. London: John Wiley, 1981. 500 p.
[2] Reinhardt CG, Krugh TR. A comparative study of ethidium bromide complexes with dinucleotides and DNA: direct evidence for intercalation and nucleic acid sequence preferences. Biochemistry. 1978;17(23):4845-54.
[3] Feigon J, Leupin W, Denny WA, Kearns DR. Binding of ethidium derivatives to natural DNA: a 300 MHz 1H NMR study. Nucleic Acids Res. 1982;10(2):749-62.
[4] Bailey SA, Graves DE, Rill R, Marsch G. Influence of DNA base sequence on the binding energetics of actinomycin D. Biochemistry. 1993;32(22):5881-7.
[5] Bailey SA, Graves DE, Rill R. Binding of actinomycin D to the T(G)nT motif of double-stranded DNA: determination of the guanine requirement in nonclassical, non-GpC binding sites. Biochemistry. 1994;33(38):11493-500.
[6] Davies DB, Djimant LN, Veselkov AN. 1 H NMR structural analysis of the interactions of proflavine with self-complementary deoxytetranucleosides of Different Base sequence. Nucleosides Nucleotides. 1994;13(1-3):637–55.
[7] Davies DB, Veselkov AN. Structural and thermodynamical analysis of molecular complexation by 1H NMR spectroscopy. Intercalation of ethidium bromide with the isomeric deoxytetranucleoside triphosphates 5?-d(GpCpGpC) and 5?-d(CpGpCpG) in aqueous solution. Faraday Trans. 1996;92(19):3545-57.
[8] 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.
[9] Veselkov AN, Devis D, Dymant LN, Parkes H. Studies of the interaction proflavine tetra deoxy ribonucleoside triphosphates d (GpCpGpC) by H-NMR spectroscopy. Mol Biol (Mosk). 1991. 26(6): 1504-16.
[10] Veselkov AN, Davies D, Djimant LN, Pakes H. Investigation of proflavine interaction with deoxytetraribonucleoside triphosphate 5'-d(ApGpCpT) in aqueous solution by the method of one- and two-dimensiobal 1H-NMR spectroscopy. Biofizika. 1992;37(1):23-33.
[11] Veselkov AN, Zavyalova OS, Djimant LN, Davies D. [Analysis of complexation of ethidium bromide with self-complementary deoxyriboanucleotide 5'-d(TGCA) by the 1H-NMR] Zh Fiz Khim. 1996; 70(9):1617-24.
[12] Albert A. The Acridines. London: Edward Arnold Publ. Ltd., 1966. 604 p.
[13] 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.
[14] Veselkov AN, Djimant LN, Karawajew L, Kulikov EL. Investigation of the aggregation of acridine dyes in aqueous solution by proton NMR. Stud Biophys. 1985;106(3):171-80.
[15] Nelson JW, Tinoco I Jr. Intercalation of ethidium ion into DNA and RNA oligonucleotides. Biopolymers. 1984;23(2):213-33.
[16] McGhee JD, von Hippel PH. Theoretical aspects of DNA-protein interactions: Co-operative and non-co-operative binding of large ligands to a one-dimensional homogeneous lattice. J Mol Biol. 1974;86(2):469–89.
[17] Giessner-Prettre C, Pullman B. Quantum mechanical calculations of NMR chemical shifts in nucleic acids. Q Rev Biophys. 1987;20(3-4):113-72.
[18] Poltev VI, Teplukhin AV. [Base interaction and conformation manifestations of repetitive nucleotide sequences]. Mol Biol (Mosk). 1987;21(1):102-15.
[19] Poltev VI, Teplukhin AV. Conformational implications of some nucleotide sequences. Int J Quant Chem. 1989;35(1):91–102.
[20] Dickerson RE. Definitions and nomenclature of nucleic acid structure parameters. J Biomol Struct Dyn. 1989;6(4):627–34.
[21] Neidle S, Achari A, Taylor GL, Berman HM, Carrell HL, Glusker JP, Stallings WC. Structure of a dinucleoside phosphate--drug complex as model for nucleic acid--drug interaction. Nature. 1977;269(5626):304-7.
[22] Berman HM, Neidle S, Stodola RK. Drug-nucleic acid interactions: conformational flexibility at the intercalation site. Proc Natl Acad Sci U S A. 1978;75(2):828-32.
[23] Searle MS. NMR studies of drug-DNA interactions. Prog Nucl Magn Reson Spectrosc. 1993; 25(5): 403-480.
[24] Pritchard NJ, Blake A, Peacocke AR. Modified intercalation model for the interaction of amino acridines and DNA. Nature. 1966;212(5068):1360-1.
[25] Kapuscinsky J, Darzynkiewiecz Z. Intercalation of acridine drugs with single-stranded DNA. J Biomol Struct Dyn. 1987; 5: 127-143.
[26] Davies DB, Baranovsky SF, Veselkov AN. Structural and thermodynamical analysis of drug binding to single-stranded DNA oligomers Self-association of non-self-complementary deoxytetranucleotides of different base sequence and their complexation with ethidium bromide in aqueous solution. Faraday Trans. 1997;93(8):1559–72.
[27] Veselkov AN, Devis D, Dymant LN. [Thermodynamic analysis of the interaction of the acridine dye proflavin with deoxytetranucleotides with various base sequences from (1)H-NMR data]. Mol Biol (Mosk). 1992;26(4):780-92.
[28] Ross PD, Subramanian S. Thermodynamics of protein association reactions: forces contributing to stability. Biochemistry. 1981;20(11):3096-102.
[29] Reinert KE. Anthracycline-binding induced DNA stiffening, bending and elongation; stereochemical implications from viscometric investigations. Nucleic Acids Res. 1983;11(10):3411-30.
[30] Veselkov AN, Zavyalova OS, Dymant LN et al. Analysis of phenatridine ethidium bromide dye complexation with deoxytetranucleotides 5'-(TpGpCpA). Zh Fiz Khim. 1997; 71(1): 24-29.