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 AJAC  Vol.4 No.12 , December 2013
Zn Ions Change Binding Mode of TOEPyP4 with DNA and Cause DNA Transition from B to C and Zn-Like Conformations
Abstract: It is known that at low concentrations of TMPyP4, this porphyrin predominantly intercalates between GC pairs at GC-rich sites of duplex DNA and G-quadruplexes of various constructions, and stabilizes these structures. However, there are still some arguable suggestions about the exact binding sites and modes of TMPyP4 to GC-rich regions of DNA in case of helation of divalent ions with help of the porphrin, which makes porphyrin structure asymmetric. We examined TOEPyP4—analogue of TMPyP4—and studied interaction of TOEPyP4 into the calf thymus DNA at presence of nanomole concentrations of one of the most important microelements in cell vital function—Zn ion. On the basis of CD and absorption spectra of the DNA-TOEPyP4 mixture, it was determined that nanomole concentrations of Zn ions changed porphyrin intercalative binding mode to some external binding modes, which initiated transition of the canonic B conformation of DNA into C-like conformation, and incubation of the (DNA-TOEP4) + Zn mixture at 37?C caused B-Z-like transition, but no transition was observed for the DNA-TOEPyP4 mixture. In particular, at 10 mM?NaCl, TOEPyP4/DNA = 0.02, the binding mode change was observed in the concentration range from 150 to 300 nM?Zn, and the B-C-like transition occurred from 150 to 600 nM?Zn. The B-Z transition at TOEPyP4/DNA = 0.015, Zn/DNA = 0.015, NaCI 10 mM, T = 37?C was observed within incubation time interval from 0.3 to 20 hours, and maximal percent of Z-like form was seen when incubation time interval was from 5 to 6 hours.    
Cite this paper: J. Monaselidze, M. Gorgoshidze, D. Khachidze, M. Kiladze, V. Bregadze, E. Kiziria, H. Margaryan and N. Hakobyan, "Zn Ions Change Binding Mode of TOEPyP4 with DNA and Cause DNA Transition from B to C and Zn-Like Conformations," American Journal of Analytical Chemistry, Vol. 4 No. 12, 2013, pp. 744-748. doi: 10.4236/ajac.2013.412090.
References

[1]   C. L. Grand, H. Han, R. M. Munoz, S. Weitman, D. D. Von Hoff, L. H. Hurley and D. J. Bearss, “The Cationic Porphyrin TMPyP4 Down-Regulates c-MYC and Human Telomerase Reverse Ttranscriptase Expression and Inhibits Tumor Growth in Vivo,” Molecular Cancer Therapeutics, Vol. 1, No. 8, 2002, pp. 565-573.

[2]   N. Nagesh and A. Ganesh Kumar, “Interaction of TMPyP4, TMPyP3, and TMPyP2 with Intramolecular G-Quadruplex Formed by Promoter Region of Bcl2 and KRAS NHPPE,” ISRN Biophysics, Vol. 2012, 2012, Article ID: 786596.

[3]   D. J. Cashman, R. Buscaglia, M. W Freyer, J. Dettler, L. H. Hurley and E. A. Lewis, “Molecular Modeling and Biophysical Analysis of the c-MYC NHE-III1 Silencer Element,” Journal of Molecular Modeling, Vol. 14, No. 2, 2008, pp. 93-101.
http://dx.doi.org/10.1007/s00894-007-0254-z

[4]   E. Izbicka, R. T. Wheelhouse, E. Raymond, K. K. Davison, R. A. Lawrence, D. Sun, B. E. Windle, L. H. Hurley and D. D. Von Hoff, “Effects of Cationic Porphyrins as G-Quadruplex Interactive Agents in Human Tumor Cells,” Cancer Research, Vol. 59, No. 3, 1999, pp. 639-644.

[5]   Z. Zhang, J. Dai, E. Veliath, R. A. Jones and D. Yang, “Structure of a Two-G-Tetrad Intramolecular G-Quadruplex Formed by a Variant Human Telomeric Sequence in K+ Solution: Insights into the Interconversion of Human Telomeric G-Quadruplex Structures,” Nucleic Acids Research, Vol. 38, No. 3, 2008, pp. 1009-1021.
http://dx.doi.org/10.1093/nar/gkp1029

[6]   J. Monaselidze, G. Majagaladze, Sh. Barbakadze, D. Khachidze, M. Gorgoshidze, Y. Kalandadze, S. Haroutiunian, Y. Dalyan and V. Vardanyan, “Microcalorimetric Investigation of DNA, Poly(Da)Poly(Dt) and Poly[D(A-C)]Poly[D(G-T)] Melting in the Presence of Water Soluble (Meso Tetra (4 N Oxyethylpyridyl) Porphyrin) and Its Zn Complex,” Journal of Biomolecular Structure and Dynamics, Vol. 25, No. 4, 2008, pp. 419-424.
http://dx.doi.org/10.1080/07391102.2008.10507190

[7]   Y. Dalyan, S. Haroutiunian, G. Ananyan, V. Vardanyan, V. Madakyan, R. Kazaryan, L. Saakyan, L. Messory, P. Orioli and A. Benight, “Interaction of Meso-Tetra-(4-N-oxyethylpyridyl) Porphyrin, Its 3-N Analog and Their Metallo-Complexes with Duplex DNA,” Journal of Biomolecular Structure and Dynamics, Vol. 18, No. 5, 2001, pp. 677-687.
http://dx.doi.org/10.1080/07391102.2001.10506698

[8]   M. J. Carlin, E. Mark and R. Fiel, “Intercalative and Nonintercalative Binding of Large Cationic Porphyrin Ligand to Polynucleorides,” Nucleic Acids Research, Vol. 11, No. 17, 1983, pp. 6141-6153.
http://dx.doi.org/10.1093/nar/11.17.6141

[9]   R. T. Fiel, “Porphyrin Nucleic Acid Interaction,” Journal of Biomolecular Structure and Dynamics, Vol. 6, No. 6, 1989, pp. 1259-1274.
http://dx.doi.org/10.1080/07391102.1989.10506549

[10]   V. I. Ivanov, L. E. Minchenkova, A. K Schyolkin and A. I. Poletoyev, “Different Conformations of Double-Stranded Nucleic Acid in Solution as Revealed by Circular Dichroism,” Biopolymers, Vol. 12, No. 1, 1973, pp. 89-110.
http://dx.doi.org/10.1002/bip.1973.360120109

[11]   K. Jaroslav, I. Kejnovská, D. Renciuk and M. Vorlícková, “Circular Dichroism and Conformational Polymorphism of DNA,” Nucleic Acids Research, Vol. 37, No. 6, 2009, pp. 1713-1725. http://dx.doi.org/10.1093/nar/gkp026

[12]   J. Monaselidze, E. Kiziria, M. Gorgoshidze, D. Khachidze, M. Kiladze, E. Lomidze, H. Margaryan and N. Hakobyan, “CD and DSC Investigation of Individual and Complex Influence of Meso-Tetra(4-Oxiethylpyridil) Por-phyrin (TOEPyP4) and Its Zn-Complex on DNA,” American Journal of Analytical Chemistry, Vol. 3, No. 10, 2012, pp. 698-703.

[13]   S. Lee, Y. A. Lee, J. Y. Lee, D. H. Kim and S. K. Kim, “Rotation of Periphery Methylpyridine of Meso-Tetrakis(n-N-Methylpyridiniumyl)Porphyrin (n = 2, 3, 4) and Its Selective Binding to Native and Synthetic DNAs,” Biophysical Journal, Vol. 83, No. 1, 2002, pp. 371-381.
http://dx.doi.org/10.1016/S0006-3495(02)75176-X

[14]   J. Monaselidze, M. Kiladze, M. Gorgoshidze, D. Khachidze, V. Bregadze, E. Lomidze and T. Lezhava, “Microcalorimetric Study of DNA-Cu(II)TOEPyP4 Porphyrin Complex,” Journal of Thermal Analysis and Calorimetry, Vol. 108, No. 1, 2012, pp. 127-131.

[15]   J. M. Dettler, R. Le. Buscaglia and E. A. Lewis, “DSC Deconvolution of the Structural Complexity of c-MYC P1 Promoter G-Quadruplexes,” Biophysical Journal, Vol. 100, No. 6, 2011, pp. 1517-1525.
http://dx.doi.org/10.1016/j.bpj.2011.01.068

[16]   M. Benett, A. Krah, F. Wien, F. Carman, R. Mekenna, M. Sanderson and S. Neidle, “A DNA-Porphyrin MinorGroove Complex at Atomic Resolution: The Structural Consequences of Porphyrin Ruffing,” Proceedings of the National Academy of Sciences, Vol. 97, No. 17, 2000, pp. 9476-9481. http://dx.doi.org/10.1073/pnas.160271897

[17]   W. Saenger, “Principles of Nucleic Acid Structure,” Springer, New York, 1984.
http://dx.doi.org/10.1007/978-1-4612-5190-3

[18]   M. A. Sari, J. P. Battioni, D. Dupré, D. Mansuy and J. B. Le Pecq, “Interaction of Cationic porphyrins with DNA: Importance of the Number and Position of the Charges and Minimum Structural Requirements for Intercalation,” Biochemistry, Vol. 29, No. 17, 1990, pp. 4205-4215.
http://dx.doi.org/10.1021/bi00469a025

[19]   T. Ohyama, H. Mita and Y. Yamamoto, “Study on the Complexation between DNA and Cationic Porphyrin Derivatives,” Nucleic Acids Symposium Series, Vol. 48, No. 1, 2004, pp. 137-138.
http://dx.doi.org/10.1093/nass/48.1.137

 
 
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