Abstract
A general model of competitive binding in drug–interceptor–DNA systems has been developed in order to quantify both the interceptor and protector mechanisms. The model involves full parameterization of the basic equations governing the mutual competition between drugs binding to DNA and incorporates as partial cases various similar models existing in the literature. The generality of the model results from strict accounting of the statistical effects of the binding of the drug and interceptor with DNA according to the McGhee-von Hippel formalism, and to the strict treatment of hetero-association between the drug and interceptor, which includes formation of all possible types of self- and hetero-complexes in solution. Indirect experimental evidence is provided for the importance of the protector mechanism in drug–caffeine–DNA systems, which is sometimes ignored in the literature because of the small magnitude of the CAF-DNA binding constant.
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Baranovsky SF, Bolotin PA, Evstigneev MP, Chernyshev DN (2008) Complexation of heterocyclic ligands with DNA in aqueous solution. J Appl Spectrosc 75:251–260
Baranovsky SF, Bolotin PA, Evstigneev MP, Chernyshev DN (2009) Interaction of ethidium bromide and caffeine with DNA in aqueous solution. J Appl Spectrosc 76:132–139
Barceló F, Capó D, Portugal J (2002) Thermodynamic characterization of the multivalent binding of chartreusin to DNA. Nucleic Acids Res 30:4567–4573
Bresloff JL, Crothers DM (1975) DNA-ethidium reaction kinetics: demonstration of direct ligand transfer between DNA binding sites. J Mol Biol 95:103–110
Chaires JB (1990) Biophysical chemistry of the daunomycin-DNA interaction. Biophys Chem 35:191–202
Davies DB, Veselkov DA, Djimant LN, Veselkov AN (2001) Hetero-association of caffeine and aromatic drugs and their competitive binding with a DNA oligomer. Eur Biophys J 30:354–366
Evstigneev MP (2010) DNA-binding aromatic drug molecules: physico-chemical interactions and their biological roles. Lambert Academic Publishing, Saarbrücken
Evstigneev MP, Mykhina YuV, Davies DB (2005) Complexation of daunomycin with a DNA oligomer in the presence of an aromatic vitamin (B2) determined by NMR spectroscopy. Biophys Chem 118:118–127
Evstigneev MP, Khomich VV, Davies DB (2006a) Complexation of anthracycline drugs with DNA in the presence of caffeine. Eur Biophys J 36:1–11
Evstigneev MP, Rybakova KA, Davies DB (2006b) Complexation of norfloxacin with DNA in the presence of caffeine. Biophys Chem 121:84–95
Evstigneev MP, Lantushenko AO, Evstigneev VP, YuV Mykhina, Davies DB (2008) Quantitation of the molecular mechanisms of biological synergism in a mixture of DNA-acting aromatic drugs. Biophys Chem 132:148–158
Evstigneev MP, Mosunov AA, Evstigneev VP, Parkes HG, Davies DB (2011a) Quantification of the interceptor action of caffeine on the in vitro biological effect of the antitumour agent topotecan. Eur Biophys J 40:969–980
Evstigneev VP, Mosunov AA, Buchelnikov AS, Hernandez Santiago AA, Evstigneev MP (2011b) Complete solution of the problem of one-dimensional non-covalent non-cooperative self-assembly in two-component systems. J Chem Phys 134:194902–194907
Fausett LV (1999) Applied numerical analysis using MATLAB. Pearson Prentice Hall, Upper Saddle River
Hernandez Santiago AA, Andrejuk DD, Cervantes Tavera AM, Davies DB, Evstigneev MP (2009) Complexation of biologically active aromatic compounds with DNA in the presence of theophylline. J Biol Phys 35:115–126
Johnson IM, Kumar SG, Malathi R (2003) De-intercalation of ethidium bromide and acridine orange by xanthine derivatives and their modulatory effect on anticancer agents: a study of DNA-directed toxicity enlightened by time correlated single photon counting. J Biomol Struct Dyn 20:677–686
Kapuscinski J, Darzynkiewicz Z (1985) Interactions of antitumor agents ametantrone and mitoxantrone (novatrone) with double-stranded DNA. Biochem Pharmacol 34:4203–4213
McGhee JD, von Hippel PH (1974) 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 86:469–489
Muñoz MA, Carmona C, Hidalgo J, Guardado P, Balón M (1995) Molecular associations of flavins with betacarbolines and related indoles. Bioorg Med Chem 3:41–47
Nechipurenko YD (1984) Cooperative effects on binding of large ligands to DNA. II. Contact cooperative interactions between bound ligand molecules. Mol Biol 18:1066–1079
Nocedal J, Wright SJ (1999) Numerical optimization. Springer, New York
Osowski A, Pietrzak M, Wieczorek Z, Wieczorek J (2010) Natural compounds in the human diet and their ability to bind mutagens prevents DNA-mutagen intercalation. J Toxicol Environ Health A 73:1141–1149
Pietrzak M, Wieczorek Z, Wieczorek J, Darzynkiewicz Z (2006) The ‘interceptor’ properties of chlorophyllin measured within the three-component system: Intercalator-DNA-chlorophyllin. Biophys Chem 123:11–19
Pietrzak M, Halicka HD, Wieczorek Z, Wieczorek J, Darzynkiewicz Z (2008) Attenuation of acridine mutagen ICR-191-DNA interactions and DNA damage by the mutagen interceptor chlorophyllin. Biophys Chem 135:69–75
Piosik J, Zdunek M, Kapuscinski J (2002) The modulation by xanthines of the DNA-damaging effect of polycyclic aromatic agents: part II. The stacking complexes of caffeine with doxorubicin and mitoxantrone. Biochem Pharmacol 63:635–646
Piosik J, Gwizdek-Wiśniewska A, Ulanowska K, Ochociński J, Czyż A, Węgrzyn G (2005) Methylxanthines (caffeine, pentoxifylline and theophylline) decrease the mutagenic effect of daunomycin, doxorubicin and mitoxantrone. Acta Biochim Pol 52:923–926
Piosik J, Wasielewski K, Woziwodzka A, Śledź W, Gwizdek-Wiśniewska A (2010) De-intercalation of ethidium bromide and propidium iodine from DNA in the presence of caffeine. Cent Eur J Biol 5:59–66
Ramu A, Mehta MM, Liu J, Turyan I, Aleksic A (2000) The riboflavin-mediated photooxidation of doxorubicin. Canc Chemother Pharmacol 46:449–458
Schwarz G, Klose S, Balthasar W (1970) Cooperative binding to linear biopolymers. 2. Thermodynamic analysis of the proflavine-poly(l-glutamic acid) system. Eur J Biochem 12:454–460
Traganos F, Kapuscinski J, Darzynkiewicz Z (1991) Caffeine modulates the effects of DNA-intercalating drugs in vitro: A flow cytometric and spectrophotometric analysis of caffeine interaction with novantrone, doxorubicin, ellipticine, and the doxorubicin analogue AD198. Cancer Res 51:3682–3689
Traganos F, Kapuscinski J, Gong JP, Ardelt B, Darzynkiewicz RJ, Darzynkiewicz Z (1993) Caffeine prevents apoptosis and cell-cycle effects induced by camptothecin or topotecan in HL-60 cells. Cancer Res 53:4613–4618
Wang H, Zou H, Zhang Y (1998) Quantitative study of competitive binding of drugs to protein by microdialysis/high-performance liquid chromatography. Anal Chem 70:373–377
Woziwodzka A, Gwizdek-Wiśniewska A, Piosik J (2011) Caffeine, pentoxifylline and theophylline form stacking complexes with IQ-type heterocyclic aromatic amines. Bioorg Chem 39:10–17
Zimmermann HW (1986) Physicochemical and cytochemical investigations on the binding of ethidium and acridine dyes to DNA and to organelles in living cells. Angew Chem 25:115–130
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This work was supported, in part, by BUAP PROMEP/103.5/07/2208 grant.
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Buchelnikov, A.S., Santiago, A.A.H., Flores, M.G. et al. General analysis of competitive binding in drug–interceptor–DNA systems. Eur Biophys J 41, 273–283 (2012). https://doi.org/10.1007/s00249-011-0783-3
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DOI: https://doi.org/10.1007/s00249-011-0783-3