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Computational evidence for structural consequences of kiteplatin damage on DNA

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Abstract

The reaction of the potential anticancer drug kiteplatin, cis-[PtCl2(cis-1,4-DACH)], with oligomers of single- and double-stranded DNA ranging from 2 to 12 base pairs in length was performed as a model for DNA interaction. The potential for conformational flexibility of single-stranded adducts was examined with density functional theory (DFT) and compared with data from 1H-NMR 1D and 2D spectroscopy. This indicates the presence of multiple conformations of an adduct with d(GpG), but only one form of the adduct with d(TGGT). The importance of a suitable theoretical model, and in particular basis set, in reproducing experimental data is demonstrated. The DFT theoretical model was extended to platinated base pair step (GG/CC), allowing a comparison to the related compounds cisplatin and oxaliplatin. Adducts of kiteplatin with larger fragments of double-stranded DNA, including tetramer, octamer, and dodecamer, were studied theoretically using hybrid quantum mechanics/molecular mechanics methods. Structural parameters of all the base-paired models were evaluated and binding energies calculated in gas phase and in solution; these are compared across the series and also with the related complexes cisplatin and oxaliplatin, thus revealing insights into how kiteplatin binds to DNA and similarities and differences between this and related compounds.

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References

  1. Rosenberg B, VanCamp L, Trosko JE, Mansour VH (1969) Platinum compounds: a new class of potent antitumour agents. Nature 222:385–386

    Article  CAS  PubMed  Google Scholar 

  2. Kelland L (2007) The resurgence of platinum-based cancer chemotherapy. Nat Rev Chem 7:573–584

    Article  CAS  Google Scholar 

  3. Wong E, Giandomenico CM (1999) Current status of platinum-based antitumor drugs. Chem Rev 99:2451–2466

    Article  CAS  PubMed  Google Scholar 

  4. Galanski M, Jakupec MA, Keppler BK (2005) Update of the preclinical situation of anticancer platinum complexes: novel design strategies and innovative analytical approaches Curr. Med Chem 12:2075–2094

    CAS  Google Scholar 

  5. van Zutphen S, Reedijk J (2005) Targeting platinum anti-tumour drugs: overview of strategies employed to reduce systemic toxicity. Coord Chem Rev 249:2845–2853

    Article  Google Scholar 

  6. Raymond E, Chaney SG, Taamma A, Cvitkovic E (1998) Oxaliplatin: a review of preclinical and clinical studies. Ann Oncol 9:1053–1071

    Article  CAS  PubMed  Google Scholar 

  7. Díaz-Rubio E, Sastre J, Zaniboni A, Labianca R, Cortés-Funes H, de Braud F, Boni C, Benavides M, Dallavalle G, Homerin M (1998) Oxaliplatin as single agent in previously untreated colorectal carcinoma patients: a phase II multicentric study. Ann Oncol 9:105–108

    Article  PubMed  Google Scholar 

  8. Wu Y, Pradhan P, Havener J, Boysen G, Swenberg JA, Campbell SL, Chaney SG (2004) NMR solution structure of an oxaliplatin 1,2-d(GG) intrastrand cross-link in a DNA dodecamer duplex. J Mol Biol 341:1251–1269

    Article  CAS  PubMed  Google Scholar 

  9. Wu Y, Bhattacharyya D, King CL, Baskerville-Abraham I, Huh SH, Boysen G, Swenberg JA, Temple B, Campbell SL, Chaney SG (2007) Solution structures of a DNA dodecamer duplex with and without a cisplatin 1,2-d(GG) intrastrand cross-link: comparison with the same DNA duplex containing an oxaliplatin 1,2-d(GG) intrastrand cross-link. Biochemistry 46:6477–6487

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Bhattacharyya D, Ramachandran S, Sharma S, Pathmasiri S, King CL, Baskerville-Abraham I, Boysen G, Swenberg JA, Campbell SL, Dokholyan NV, Chaney SG (2011) Flanking bases influence the nature of DNA distortion by platinum 1,2-intrastrand (GG) cross-links. PLoS one 6:e23582

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  11. Hoeschele JD, Showalter HD, Kraker AJ, Elliott WL, Roberts BJ, Kampf JW (1994) Synthesis, structural characterization, and antitumor properties of a novel class of large-ring platinum(II) chelate complexes incorporating the cis-1,4-diaminocyclohexane ligand in a unique locked boat conformation. J Med Chem 37:2630–2636

    Article  CAS  PubMed  Google Scholar 

  12. Margiotta N, Marzano C, Gandin V, Osella D, Ravera M, Gabano E, Platts JA, Petruzzella E, Hoeschele JD, Natile G (2012) Revisiting [PtCl2(cis-1,4-DACH)]: an underestimated antitumor drug with potential application to the treatment of oxaliplatin-refractory colorectal cancer. J Med Chem 55:7182–7192

    Article  CAS  PubMed  Google Scholar 

  13. Ranaldo R, Margiotta N, Intini FP, Pacifico C, Natile G (2008) Conformer distribution in (cis-1,4-DACH) bis(guanosine-5′-phosphate)platinum(II) adducts: a reliable model for DNA adducts of antitumoral cisplatin. Inorg Chem 47:2820–2830

    Article  CAS  PubMed  Google Scholar 

  14. Brabec V, Malina J, Margiotta N, Natile G, Kasparkova J (2012) Thermodynamic and mechanistic insights into translesion dna synthesis catalyzed by y-family dna polymerase across a bulky double-base lesion of an antitumor platinum drug. Chem Eur J 18:15439–15448

    Article  CAS  PubMed  Google Scholar 

  15. Kasparkova J, Suchankova T, Halamikova A, Zerzankova L, Vrana O, Margiotta N, Natile G, Brabec V (2010) Cytotoxicity, cellular uptake, glutathione and DNA interactions of an antitumor large-ring Pt II chelate complex incorporating the cis-1,4-diaminocyclohexane carrier ligand. Biochem Pharmacol 79:552–564

    Article  CAS  PubMed  Google Scholar 

  16. Sherman SE, Gibson D, Wang AH, Lippard SJ (1985) X-ray structure of the major adduct of the anticancer drug cisplatin with DNA: cis-[Pt(NH3)2(d(pGpG))]. Science 230:412–417

    Article  CAS  PubMed  Google Scholar 

  17. Margiotta N, Petruzzella E, Platts JA, Mutter ST, Deeth RJ, Ranaldo R, Papadia P, Marzilli PA, Marzilli LG, Hoeschele JD Natile G (2014) DNA fragment conformations in adducts with Kiteplatin. Dalton Trans. doi:10.1039/c4dt01796j (in press)

  18. Banáš P, Jurečka P, Walter NG, Šponer J, Otyepka M (2009) Theoretical studies of RNA catalysis: hybrid QM/MM methods and their comparison with MD and QM. Methods 49:202–216

    Article  PubMed Central  PubMed  Google Scholar 

  19. Basch H, Krauss M, Stevens WJ, Cohen D (1985) Binding of Pt(NH3) 2+3 to nucleic acid bases. Inorg Chem 24:3313–3317

    Article  CAS  Google Scholar 

  20. Carloni P, Andreoni W, Hutter J, Curioni A, Giannozzi P, Parinello M (1995) Structure and bonding in cisplatin and other Pt(II) complexes. Chem Phys Lett 234:50–56

    Article  CAS  Google Scholar 

  21. Pavankumar PNV, Seetharamulu P, Yao S, Saxe JD, Reddy DG, Hausheer FH (1999) Comprehensive ab initio quantum mechanical and molecular orbital (MO) analysis of cisplatin: structure, bonding, charge density, and vibrational frequencies. J Comput Chem 20:365–382

    Article  CAS  Google Scholar 

  22. Baik MH, Friesner RA, Lippard SJ (2003) Theoretical study of cisplatin binding to purine bases: why does cisplatin prefer guanine over adenine? J Am Chem Soc 125:14082–14092

    Article  CAS  PubMed  Google Scholar 

  23. Monnet J, Kozelka J (2012) Cisplatin GG-crosslinks within single-stranded DNA: origin of the preference for left-handed helicity. J Inorg Biochem 115:106–112

    Article  CAS  PubMed  Google Scholar 

  24. Sarmah P, Deka RC (2008) Solvent effect on the reactivity of cis-platinum (II) complexes: a density functional approach. Int J Quantum Chem 108:1400–1409

    Article  CAS  Google Scholar 

  25. Zhu C, Raber J, Eriksson LA (2005) Hydrolysis process of the second generation platinum-based anticancer drug cis-amminedichlorocyclohexylamineplatinum (II). J Phys Chem B 109:12195–12205

    Article  CAS  PubMed  Google Scholar 

  26. Gkionis K, Platts JA (2012) Comp. QM/MM studies of cisplatin complexes with DNA dimer and octamer. Theor Chem 993:60–65

    Article  CAS  Google Scholar 

  27. Gkionis K, Mutter S, Platts JA (2013) QM/MM description of platinum–DNA interactions: comparison of binding and DNA distortion of five drugs. RSC Advances 3:4066–4073

    Article  CAS  Google Scholar 

  28. Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery Jr JA, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Keith T, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas O, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ (2010) Gaussian 09, Revision C.01. Gaussian, Inc., Wallingford

  29. Grimme S (2006) Semiempirical GGA-type density functional constructed with a long-range dispersion correction. J Comp Chem 27:1787–1799

    Article  CAS  Google Scholar 

  30. Weigend F, Ahlrichs R (2005) Balanced basis sets of split valence, triple zeta valence and quadruple zeta valence quality for H to Rn: design and assessment of accuracy. Phys Chem Chem Phys 7:3297–3305

    Article  CAS  PubMed  Google Scholar 

  31. Klamt A, Schuurmann G (1993) COSMO: a new approach to dielectric screening in solvents with explicit expressions for the screening energy and its gradient. J Chem Soc Perkin Trans 2:799–805

  32. Vreven T, Byun KS, Komáromi I, Dapprich S, Montgomery JA Jr, Morokuma K, Frisch MJ (2006) Combining quantum mechanics methods with molecular mechanics methods in ONIOM. J Chem Theory Comput 2:815–826

    Article  CAS  Google Scholar 

  33. Ditchfield R, Hehre WJ, Pople JA (1971) Self-consistent molecular orbital methods. 9. Extended Gaussian-type basis for molecular-orbital studies of organic molecules. J Chem Phys 54:724–729

    Article  CAS  Google Scholar 

  34. Cornell WD, Cieplak P, Bayly CI, Gould IR, Merz KM Jr, Ferguson DM, Spellmeyer DC, Fox T, Caldwell JW, Kollman PA (1995) A second generation force-field for the simulation of proteins, nucleic-acids, and organic-molecules. J Am Chem Soc 117:5179–5197

    Article  CAS  Google Scholar 

  35. Li X, Frisch MJ (2006) Energy-represented DIIS within a hybrid geometry optimization method. J Chem Theory Comput 2:835–839

    Article  CAS  Google Scholar 

  36. Barone V, Cossi M (1998) Quantum calculation of molecular energies and energy gradients in solution by a conductor solvent model. J Phys Chem A 102:1995–2001

    Article  CAS  Google Scholar 

  37. http://w3dna.rutgers.edu/. Accessed 1 Nov 2013

  38. Dodd LR, Theodorou DN (1991) Analytical treatment of the volume and surface area of molecules formed by an arbitrary collection of unequal spheres intersected by planes. Mol Phys 72:1313–1345

    Article  CAS  Google Scholar 

  39. Natile G, Marzilli LG (2006) Non-covalent interactions in adducts of platinum drugs with nucleobases in nucleotides and DNA as revealed by using chiral substrates. Coord Chem Rev 250:1315–1331

    Article  CAS  Google Scholar 

  40. Hay PJ, Wadt WR (1985) Ab initio effective core potentials for molecular calculations—potentials for the transition-metal atoms Sc to Hg. J Chem Phys 82:270–283

    Article  CAS  Google Scholar 

  41. Andrae D, Haeussermann U, Dolg M, Stoll H, Preuss H (1990) Energy-adjusted ab initio pseudopotentials for the 2nd and 3rd row transition-elements. Theor Chem Acc 77:123–141

    Article  CAS  Google Scholar 

  42. Ditchfield R, Hehre WJ, Pople JA (1971) Self-consistent molecular orbital methods. 9. Extended Gaussian-type basis for molecular-orbital studies of organic molecules. J Chem Phys 54:724

    Article  CAS  Google Scholar 

  43. Hehre WJ, Ditchfield R, Pople JA (1972) Self-consistent molecular orbital methods. 12. Further extensions of Gaussian-type basis sets for use in molecular-orbital studies of organic-molecules. J Chem Phys 56:2257

    Article  CAS  Google Scholar 

  44. Hariharan PC, Pople JA (1973) Influence of polarization functions on molecular-orbital hydrogenation energies. Theor Chem Acc 28:213–222

    Article  CAS  Google Scholar 

  45. Becke AD (1988) Density-functional exchange-energy approximation with correct asymptotic-behavior. Phys Rev A 38:3098–3100

    Article  CAS  PubMed  Google Scholar 

  46. Lee C, Yang W, Parr RG (1988) Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys Rev B 37:785–789

    Article  CAS  Google Scholar 

  47. Becke AD (1993) Density-functional thermochemistry. III. The role of exact exchange. J Chem Phys 98:5648–5652

    Article  CAS  Google Scholar 

  48. Becke AD (1993) A new mixing of Hartree-Fock and local density-functional theories. J Chem Phys 98:1372–1377

    Article  CAS  Google Scholar 

  49. Zhao Y, Truhlar DG (2008) The M06 suite of density functionals for main group thermochemistry, thermochemical kinetics, noncovalent interactions, excited states, and transition elements: two new functionals and systematic testing of four M06-class functionals and 12 other functionals. Theor Chem Acc 120:215–241

    Article  CAS  Google Scholar 

  50. Chai JD, Head-Gordon M (2008) Long-range corrected hybrid density functionals with damped atom-atom dispersion corrections. Phys Chem Chem Phys 10:6615–6620

    Article  CAS  PubMed  Google Scholar 

  51. Arunan E, Desiraju GR, Klein RA, Sadlej J, Scheiner S, Alkorta I, Clary DC, Crabtree RH, Dannenberg JJ, Hobza P, Kjaergaard HG, Legon AC, Mennucci B, Nesbitt DJ (2011) Defining the hydrogen bond: an account. Pure Appl Chem 83:1619–1636

    CAS  Google Scholar 

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Acknowledgments

We acknowledge the University of Bari (Italy), the Italian Ministero dell’Università e della Ricerca (MIUR), the Fondo per gli investimenti della Ricerca di Base (FIRB RINAME RBAP114AMK), the European Union (COST CM1105, Functional metal complexes that bind to biomolecules) and the Inter-University Consortium for Research on the Chemistry of Metal Ions in Biological Systems (C. I. R. C. M. S. B.) for support.

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Authors and Affiliations

  1. School of Chemistry, Cardiff University, Park Place, Cardiff, CF10 3AT, UK

    Shaun T. Mutter & James A. Platts

  2. Department of Chemistry, University of Bari Aldo Moro, Via E. Orabona 4, 70125, Bari, Italy

    Nicola Margiotta

  3. Department of Biotechnology and Environmental Sciences, University of Salento, via Monteroni, 73100, Lecce, Italy

    Paride Papadia

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  1. Shaun T. Mutter
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  2. Nicola Margiotta
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  4. James A. Platts
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Correspondence to James A. Platts.

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Mutter, S.T., Margiotta, N., Papadia, P. et al. Computational evidence for structural consequences of kiteplatin damage on DNA. J Biol Inorg Chem 20, 35–48 (2015). https://doi.org/10.1007/s00775-014-1207-5

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