The Effect of Temperature on the Interaction of Phenanthroline-based Ligands with G-quadruplex: In Silico Viewpoint

Author(s): Mohadeseh Bazoobandi, Mohammad R. Bozorgmehr*, Ali Mahmoudi, Ali Morsali.

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

Volume 22 , Issue 8 , 2019

Become EABM
Become Reviewer

Abstract:

Aim and Objective: The stability of the G-quadruplex structure can increase its activity in telomerase inhibiting cancer cells. In this study, a molecular dynamics simulation method was used to study the effect of three phenanthroline-based ligands on the structure of G-quadruplex at the temperatures of 20, 40, 60 and 80°C.

Materials and Methods: RMSD values and frequency of calculated RMSD in the presence and absence of ligands show that ligands cause the relative stability of the G-quadruplex, particularly at low temperatures. The calculation of hydrogen bonds in Guanine-tetrads in three different quadruplex sheets shows that the effect of ligands on the sheets is not the same so that the bottom sheet of G-quadruplex is most affected by the ligands at high temperatures, and the Guaninetetrads in this sheet are far away. Conformation factor was calculated as a measure of ligands binding affinity for each of the G-quadruplex residues.

Results: The results show that the studied ligands interact more with the G-quadruplex than loop areas, although with increasing temperature, the binding area also includes the G-quadruplex sheets. The contribution of each of the residues involved in the G-quadruplex binding area with ligands was also calculated.

Conclusion: The calculations performed are consistent with the previous experimental observations that can help to understand the molecular mechanism of the interaction of phenanthroline and its derivatives with quadruplex.

Keywords: Phenanthroline, quadruplex, affinity, conformation factor, molecular mechanism, cancer cells.

[1]
Chiorcea-Paquim, A-M.; Eritja, R.; Oliveira-Brett, A.M. Electrochemical and AFM characterization of G-Quadruplex electrochemical biosensors and applications. J. Nucleic Acids, 2018, 2018 Article ID 5307106
[2]
Murat, P.; Singh, Y.; Defrancq, E. Methods for investigating G-quadruplex DNA/ligand interactions. Chem. Soc. Rev., 2011, 40(11), 5293-5307.
[http://dx.doi.org/10.1039/c1cs15117g] [PMID: 21720638]
[3]
Jaumot, J.; Gargallo, R. Experimental methods for studying the interactions between G-quadruplex structures and ligands. Curr. Pharm. Des., 2012, 18(14), 1900-1916.
[http://dx.doi.org/10.2174/138161212799958486] [PMID: 22376108]
[4]
Arola, A.; Vilar, R. Stabilisation of G-quadruplex DNA by small molecules. Curr. Top. Med. Chem., 2008, 8(15), 1405-1415.
[http://dx.doi.org/10.2174/156802608786141106] [PMID: 18991726]
[5]
Agarwal, T.; Roy, S.; Chakraborty, T.K.; Maiti, S. Selective targeting of G-quadruplex using furan-based cyclic homooligopeptides: Effect on c-MYC expression. Biochemistry, 2010, 49(38), 8388-8397.
[http://dx.doi.org/10.1021/bi1005927] [PMID: 20712380]
[6]
Ma, D-L.; Che, C-M.; Yan, S-C. Platinum(II) complexes with dipyridophenazine ligands as human telomerase inhibitors and luminescent probes for G-quadruplex DNA. J. Am. Chem. Soc., 2009, 131(5), 1835-1846.
[http://dx.doi.org/10.1021/ja806045x] [PMID: 18998644]
[7]
Wang, P.; Leung, C.H.; Ma, D.L.; Yan, S.C.; Che, C.M. Structure-based design of platinum(II) complexes as c-myc oncogene down-regulators and luminescent probes for G-quadruplex DNA. Chemistry, 2010, 16(23), 6900-6911.
[http://dx.doi.org/10.1002/chem.201000167] [PMID: 20437426]
[8]
Shi, S.; Geng, X.; Zhao, J.; Yao, T.; Wang, C.; Yang, D.; Zheng, L.; Ji, L. Interaction of [Ru(bpy)2(dppz)]2+ with human telomeric DNA: preferential binding to G-quadruplexes over i-motif. Biochimie, 2010, 92(4), 370-377.
[http://dx.doi.org/10.1016/j.biochi.2010.01.003] [PMID: 20096325]
[9]
Sun, J.; An, Y.; Zhang, L.; Chen, H-Y.; Han, Y.; Wang, Y-J.; Mao, Z-W.; Ji, L-N. Studies on synthesis, characterization, and G-quadruplex binding of Ru(II) complexes containing two dppz ligands. J. Inorg. Biochem., 2011, 105(2), 149-154.
[http://dx.doi.org/10.1016/j.jinorgbio.2010.10.005] [PMID: 21194612]
[10]
Ren, L.; Zhang, A.; Huang, J.; Wang, P.; Weng, X.; Zhang, L.; Liang, F.; Tan, Z.; Zhou, X. Quaternary ammonium zinc phthalocyanine: inhibiting telomerase by stabilizing G quadruplexes and inducing G-quadruplex structure transition and formation. ChemBioChem, 2007, 8(7), 775-780.
[http://dx.doi.org/10.1002/cbic.200600554] [PMID: 17361982]
[11]
Del Toro, M.; Bucek, P.; Aviñó, A.; Jaumot, J.; González, C.; Eritja, R.; Gargallo, R. Targeting the G-quadruplex-forming region near the P1 promoter in the human BCL-2 gene with the cationic porphyrin TMPyP4 and with the complementary C-rich strand. Biochimie, 2009, 91(7), 894-902.
[http://dx.doi.org/10.1016/j.biochi.2009.04.012] [PMID: 19401211]
[12]
del Toro, M.; Gargallo, R.; Eritja, R.; Jaumot, J. Study of the interaction between the G-quadruplex-forming thrombin-binding aptamer and the porphyrin 5,10,15,20-tetrakis-(N-methyl-4-pyridyl)-21,23H-porphyrin tetratosylate. Anal. Biochem., 2008, 379(1), 8-15.
[http://dx.doi.org/10.1016/j.ab.2008.04.044] [PMID: 18492481]
[13]
Arora, A.; Maiti, S. Stability and molecular recognition of quadruplexes with different loop length in the absence and presence of molecular crowding agents. J. Phys. Chem. B, 2009, 113(25), 8784-8792.
[http://dx.doi.org/10.1021/jp809486g] [PMID: 19480441]
[14]
Dutikova, Y.V.; Borisova, O.; Shchyolkina, A.; Lin, J.; Huang, S.; Shtil, A.; Kaluzhny, D. 5, 10, 15, 20-Tetra-(N-methyl-3-pyridyl) porphyrin destabilizes the antiparallel telomeric quadruplex d (TTAGGG) 4. Mol. Biol., 2010, 44(5), 823-831.
[http://dx.doi.org/10.1134/S0026893310050201]
[15]
Brossi, A. The Alkaloids. Chemistry and Pharmacology. Academic Press, 1985, Vol 25, 1-355.
[16]
Villar-Garcia, I.J.; Abebe, A.; Chebude, Y. 1, 10-Phenanthrolinium ionic liquids exhibiting excellent solubility for metal complexes: Potential solvents for biphasic and supported ionic liquid phase (SILP) catalysis. Inorg. Chem. Commun., 2012, 19, 1-3.
[http://dx.doi.org/10.1016/j.inoche.2012.01.014]
[17]
Musetti, C.; Lucatello, L.; Bianco, S.; Krapcho, A.P.; Cadamuro, S.A.; Palumbo, M.; Sissi, C. Metal ion-mediated assembly of effective phenanthroline-based G-quadruplex ligands. Dalton Trans., 2009, 2009(19), 3657-3660.
[http://dx.doi.org/10.1039/b904630p] [PMID: 19417927]
[18]
De Cian, A.; Delemos, E.; Mergny, J-L.; Teulade-Fichou, M-P.; Monchaud, D. Highly efficient G-quadruplex recognition by bisquinolinium compounds. J. Am. Chem. Soc., 2007, 129(7), 1856-1857.
[http://dx.doi.org/10.1021/ja067352b] [PMID: 17260991]
[19]
Reed, J.E.; Neidle, S.; Vilar, R. Stabilisation of human telomeric quadruplex DNA and inhibition of telomerase by a platinum-phenanthroline complex. Chem. Commun. (Camb.), 2007, 2007(42), 4366-4368.
[http://dx.doi.org/10.1039/b709898g] [PMID: 17957288]
[20]
Wang, L.; Wen, Y.; Liu, J.; Zhou, J.; Li, C.; Wei, C. Promoting the formation and stabilization of human telomeric G-quadruplex DNA, inhibition of telomerase and cytotoxicity by phenanthroline derivatives. Org. Biomol. Chem., 2011, 9(8), 2648-2653.
[http://dx.doi.org/10.1039/c0ob00961j] [PMID: 21347502]
[21]
Wang, J-T.; Zheng, X-H.; Xia, Q.; Mao, Z-W.; Ji, L-N.; Wang, K. 1,10-Phenanthroline platinum(II) complex: A simple molecule for efficient G-quadruplex stabilization. Dalton Trans., 2010, 39(31), 7214-7216.
[http://dx.doi.org/10.1039/c0dt00211a] [PMID: 20593090]
[22]
Cao, Q.; Li, Y.; Freisinger, E.; Qin, P.Z.; Sigel, R.K.; Mao, Z-W. G-quadruplex DNA targeted metal complexes acting as potential anticancer drugs. Inorg. Chem. Front., 2017, 4(1), 10-32.
[http://dx.doi.org/10.1039/C6QI00300A]
[23]
König, S.L.; Evans, A.C.; Huppert, J.L. Seven essential questions on G-quadruplexes. Biomol. Concepts, 2010, 1(2), 197-213.
[http://dx.doi.org/10.1515/bmc.2010.011] [PMID: 25961997]
[24]
Maizels, N.; Gray, L.T. The G4 genome. PLoS Genet., 2013, 9(4)e1003468
[http://dx.doi.org/10.1371/journal.pgen.1003468] [PMID: 23637633]
[25]
Piazza, A.; Adrian, M.; Samazan, F.; Heddi, B.; Hamon, F.; Serero, A.; Lopes, J.; Teulade-Fichou, M.P.; Phan, A.T.; Nicolas, A. Short loop length and high thermal stability determine genomic instability induced by G-quadruplex-forming minisatellites. EMBO J., 2015, 34(12), 1718-1734.
[http://dx.doi.org/10.15252/embj.201490702] [PMID: 25956747]
[26]
Lane, A.N.; Chaires, J.B.; Gray, R.D.; Trent, J.O. Stability and kinetics of G-quadruplex structures. Nucleic Acids Res., 2008, 36(17), 5482-5515.
[http://dx.doi.org/10.1093/nar/gkn517] [PMID: 18718931]
[27]
Nový, J.; Böhm, S.; Králová, J.; Král, V.; Urbanová, M. Formation and temperature stability of G-quadruplex structures studied by electronic and vibrational circular dichroism spectroscopy combined with ab initio calculations. Biopolymers, 2008, 89(2), 144-152.
[http://dx.doi.org/10.1002/bip.20875] [PMID: 17960602]
[28]
Parkinson, G.N.; Lee, M.P.; Neidle, S. Crystal structure of parallel quadruplexes from human telomeric DNA. Nature, 2002, 417(6891), 876-880.
[http://dx.doi.org/10.1038/nature755] [PMID: 12050675]
[29]
Lindorff-Larsen, K.; Piana, S.; Palmo, K.; Maragakis, P.; Klepeis, J.L.; Dror, R.O.; Shaw, D.E. Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins, 2010, 78(8), 1950-1958.
[http://dx.doi.org/10.1002/prot.22711] [PMID: 20408171]
[30]
Macke, T. J.; Svrcek-Seiler, W.; Brown, R. A.; Kolossváry, I.; Bomble, Y. J.; Case, D. A.; Zhang, W.; Hou, T.; Schafmeister, C.; Ross, W. S. AmberTools Users’ Manual. Ver: 2010.
[31]
Chow, M.S.; Liu, L.V.; Solomon, E.I. Further insights into the mechanism of the reaction of activated bleomycin with DNA. Proc. Natl. Acad. Sci. USA, 2008, 105(36), 13241-13245.
[http://dx.doi.org/10.1073/pnas.0806378105] [PMID: 18757754]
[32]
Bussi, G.; Donadio, D.; Parrinello, M. Canonical sampling through velocity rescaling. J. Chem. Phys., 2007, 126(1) 014101
[http://dx.doi.org/10.1063/1.2408420] [PMID: 17212484]
[33]
Berendsen, H.J.; Postma, J.P.M.; van Gunsteren, W.F.; DiNola, A.; Haak, J. Molecular dynamics with coupling to an external bath. J. Chem. Phys., 1984, 81(8), 3684-3690.
[http://dx.doi.org/10.1063/1.448118]
[34]
Hess, B.; Bekker, H.; Berendsen, H.J.; Fraaije, J.G. LINCS: A linear constraint solver for molecular simulations. J. Comput. Chem., 1997, 18(12), 1463-1472.
[http://dx.doi.org/10.1002/(SICI)1096-987X(199709)18:12<1463: AID-JCC4>3.0.CO;2-H]
[35]
Darden, T.; York, D.; Pedersen, L. Particle mesh Ewald: An N⋅ log (N) method for Ewald sums in large systems. J. Chem. Phys., 1993, 98(12), 10089-10092.
[http://dx.doi.org/10.1063/1.464397]
[36]
Parvaee, E.; Bozorgmehr, M.R.; Morsali, A. Role of repulsive forces on self-assembly behavior of amyloid β-peptide (1-40): Molecular dynamics simulation approach. Physica A, 2019, 513, 524-535.
[http://dx.doi.org/10.1016/j.physa.2018.09.034]
[37]
Housaindokht, M.R.; Bozorgmehr, M.R.; Bahrololoom, M. Analysis of ligand binding to proteins using molecular dynamics simulations. J. Theor. Biol., 2008, 254(2), 294-300.
[http://dx.doi.org/10.1016/j.jtbi.2008.04.036] [PMID: 18599089]
[38]
Kumari, R.; Kumar, R.; Lynn, A.; Lynn, A. g_mmpbsa--a GROMACS tool for high-throughput MM-PBSA calculations. J. Chem. Inf. Model., 2014, 54(7), 1951-1962.
[http://dx.doi.org/10.1021/ci500020m] [PMID: 24850022]
[39]
Karami, M.; Jalali, C.; Mirzaie, S. Combined virtual screening, MMPBSA, molecular docking and dynamics studies against deadly anthrax: An in silico effort to inhibit Bacillus anthracis nucleoside hydrolase. J. Theor. Biol., 2017, 420, 180-189.
[http://dx.doi.org/10.1016/j.jtbi.2017.03.010] [PMID: 28300596]
[40]
Verdian Doghaei, A.; Housaindokht, M.R.; Bozorgmehr, M.R. Molecular crowding effects on conformation and stability of G-quadruplex DNA structure: Insights from molecular dynamics simulation. J. Theor. Biol., 2015, 364, 103-112.
[http://dx.doi.org/10.1016/j.jtbi.2014.09.015] [PMID: 25242297]
[41]
Subashini, M.; Devarajan, P.V.; Sonavane, G.S.; Doble, M. Molecular dynamics simulation of drug uptake by polymer. J. Mol. Model., 2011, 17(5), 1141-1147.
[http://dx.doi.org/10.1007/s00894-010-0811-8] [PMID: 20686909]
[42]
Rodríguez, M.H.; Morales, L.G.F.; Basurto, J.C.; Hernández, M.C.R. Molecular docking and molecular dynamics simulation to evaluate compounds that avoid the amyloid beta 1-42 aggregation. Comput. Model. Drugs Against Alzheimer’s Dis., 2018, 132, 229-248.
[http://dx.doi.org/10.1007/978-1-4939-7404-7_9]
[43]
Chung, W.J.; Heddi, B.; Hamon, F.; Teulade-Fichou, M.P.; Phan, A.T. Solution structure of a G-quadruplex bound to the bisquinolinium compound Phen-DC(3). Angew. Chem. Int. Ed. Engl., 2014, 53(4), 999-1002.
[http://dx.doi.org/10.1002/anie.201308063] [PMID: 24356977]
[44]
Haider, S.M.; Parkinson, G.N.; Neidle, S. Structure of a G-quadruplex-ligand complex. J. Mol. Biol., 2003, 326(1), 117-125.
[http://dx.doi.org/10.1016/S0022-2836(02)01354-2] [PMID: 12547195]
[45]
Cuesta, J.; Read, M.A.; Neidle, S. The design of G-quadruplex ligands as telomerase inhibitors. Mini Rev. Med. Chem., 2003, 3(1), 11-21.
[http://dx.doi.org/10.2174/1389557033405502] [PMID: 12570851]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 22
ISSUE: 8
Year: 2019
Page: [546 - 554]
Pages: 9
DOI: 10.2174/1386207322666191022142629
Price: $65

Article Metrics

PDF: 23
HTML: 4