6-azacytidine binding to DNA molecules
Keywords:
DNA, 6AZC, spectrophotometry, numerical methods of binding parameters calculation in ligand-DNA system
Abstract
The work is dedicated to experimental study of interactions between biologically active ligand namely 6-azacitidine (6AZC) and DNA molecules. The work is carried out by a combination of spectrophotometric titration in Vis and UV regions and numerical calculations of parameters of binding in ligand-DNA systems. Two types of mixtures are considered: 6AZC-DNA and 6AZC - DNA - EB. The parameters of 6AZC binding to DNA matrixes were obtained by fitting the experimentally obtained titration curves by appropriate theoretical models using optimization programs (DALS, COMP and DALSMOD). The chosen optimal models are the ones giving the best conformity of the calculated intensities of absorption of the study mixture at several wave lengths to the ones obtained experimentally. Another criterion for selection of the optimal model is the minimal value of the Hamilton's factor. The parameters of binding that are calculated with help of the models include association constants, binding site size, molar extinction coefficients etc.The binding parameters in the 6AZC-DNA systems were calculated by the DALS program. It was shown that 6AZC interacts with native and partially damaged DNA molecules. The binding parameters in the 6AZC - DNA - EB mixture were determined by COMP and DALSMOD programs. The highest value of binding constant was found to be for the mixture 6AZC - DNA - EB.
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References
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3. Абдуллаева М.В., Фролов А.Ф., Алексеева И.В., Пальчиковская Л.И., ФедороваН.Е. Ингибирующее действие 6-азацитидина на цитомегаловирусную инфекцию человека в клеточной системе // Біополімери і клітина. – 2004. – T. 20. № 4. – С. 337 – 342.
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5. Samijlenko S.P., Alexeeva I.V., Palchykivs’ka L.H. и др. 1H NMR investigation on 6-azacytidine and its derivatives // Spectrochimica Acta Part A. – 1999. – V.55. – P. 1133 – 1141.
6. Пальчиковськая Л.Г., Платонов М.O., Aлексеева И.В. Механізм взаємодії N-1 глікозидів 6-азацитозину з каталітичним сайтом ДНК-залежної РНК полімерази фагу Т7: модельне неемпіричне квантово-хімічне дослідження // Біополімери і клітина. – 2005. – Т. 21. № 6. – С. 561 – 563.
7. Genotoxicity of not directly DNA damaging compounds //http://default/centreformolec/ejgt/stopper.doc.
8. Круглова Е.Б. Спектрофотометрический анализ поведения растворов ДНк в воде и при низких ионных силах// Биополимеры и клетка. – 1992. – Т. 8. №.1 – С. 56 –62.
9. E.B.Kruglova, N.А.Gladkovskaya. Comparison of the binding of the therapeutically active nucleosides to DNA molecules with different level of lesions// The International Society for Optical Engineering. Proceedings of SPIE. - 2002. - V 4938. - P. 241 – 245.
10. Bresloff J.L., Crothers D.M. DNA-ethidium reaction kinetics: demonstration of direct ligand transfer between DNA binding sites // J. Mol. Biol. – 1975. – V.95. – P. 103 – 123.
11. Karapetian A.T., Vardevanian P.O., Tarzikian G.A., Frank-Kamenetskii M.D. Theory of helix-coil transition on DNA-ligand complexes: the effect to two types of interaction of ligand on the parameters of transition// J. Biomol. Struct. Dyn. – 1990. – V. 8(1). –P. 123-30.
12. Hartley F., Burgess C., Alcock R. Solution equlibria. - Ellis Horwood. - 1980. - 360 p.
13. Iermak Ie.L., Kruglova O.B., Palchykovska L.H., Alexeeva I.V. Spectrophotometrical study of mechanisms of binding of cytidine analogues and ethidium bromide with DNA // Вiopolymers and cell. – 2007. – V. 23. № 6. – Р.529 – 536.
14. McGhee J.D., von Hippel P.H. Theoretical aspects of DNA-Protein interactions: Cooperative and non-cooperative binding of large ligands to a one-dimensional homogeneous lattice// J. Mol. Biol.- 1974. – V. 86. - P. 469-489.
15. Е.Б. Круглова, Н.А. Гладковская, В.Я. Малеев Использование метода спектрофотометрического анализа для вычисления термодинамических параметров связывания в системах актиноциновые производные – ДНК// Биофизика. -2005. – T. 50. - В.2. - C. 253-264
16. Круглова Е.Б., Ермак Е.Л. Конкурентное связывание двух лигандов: актиноцинового производного и кофеина с полирибоцитидиловой кислотой в разных конформационных состояниях// Вісн. XHУ. - № 637. Біофіз. Вісн. – 2004. -№ 1-2 (14). - С.32-38.
17. Di Marco A., Arcamone F. DNA complexing antibiotics: daunomycin, adriamycin and their derivatives//Arzneimittelforschung. (Drug Res.). – 1975.- V. 25(3). – P. 368-374.
18. Vologodskii A. Exploiting circular DNA// Proc. Natl. Acad. Sci. USA. - 1998.- Vol. 95. - P. 4092–4093.
19. Graves D. E., Velea L. M. Intercalative binding of small molecules to nucleic acids// Curr. Org. Chem.- 2000. -V. 4. – P. 915 - 929.
20. Winkle S.A., Rosenberg L.S., Krugh T.R. On the cooperative and noncooperative binding of ethidium to DNA // Nucleic Acids Res. – 1982. – V. 10. – P. 8211 – 8223.
21. Vardevanyan P.O., Antonyan A.P., Parsadanyan M.A., Davtyan H.G., Boyajyan Z.R., Karapetian A.T. Complex-formation of ethidium bromide with poly[d(A-T)*poly[d(A-T)] // J. Biomol. Struct. Dyn. – 2005. – V. 22. – P. 465 – 470.
22. Fox K.R., Michael J., Waring M.J. Footprinting at low temperatures: evidence that ethidium and other simple intercalators can discriminate between different nucleotide sequences // Nucleic Acids Res. – 1987. – V. 15. – P. 491–507.
Cited
How to Cite
Gladkovskaya, N. A., Ermak, Y. L., Kruglova, E. B., Palchikovskaya, L. I., & Alexeeva, I. V. (1). 6-azacytidine binding to DNA molecules. Biophysical Bulletin, 2(21), 19-28. Retrieved from https://periodicals.karazin.ua/biophysvisnyk/article/view/9579
Section
Molecular biophysics
Copyright (c) 2017 N. A. Gladkovskaya, Ye. L. Ermak, E. B. Kruglova, L. I. Palchikovskaya, I. V. Alexeeva
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