Skip to main content
SpringerLink
Log in

Ruthenium versus platinum: interactions of anticancer metallodrugs with duplex oligonucleotides characterised by electrospray ionisation mass spectrometry

  • Original Paper
  • Published:
JBIC Journal of Biological Inorganic Chemistry Aims and scope Submit manuscript

Abstract

The binding of the ruthenium-based anticancer drug candidates KP1019, NAMI-A and RAPTA-T towards different double-stranded oligonucleotides was probed by electrospray ionisation mass spectrometry and compared with that of the widely used platinum-based chemotherapeutics cisplatin, carboplatin and oxaliplatin. It was found that the extent of adduct formation decreased in the following order: cisplatin > oxaliplatin > NAMI-A > RAPTA-T > carboplatin > KP1019. In addition to the characterisation of the adducts formed with the DNA models, the binding sites of the metallodrugs on the oligonucleotides were elucidated employing top-down tandem mass spectrometry and were found to be similar for all the metallodrugs studied, irrespective of the sequence of the oligonucleotide. A strong preference for guanine residues was established.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Lippert B (1999) Cisplatin. Chemistry and biochemistry of a leading anticancer drug. VHCA, Zurich

    Book  Google Scholar 

  2. Dyson PJ, Sava G (2006) Dalton Trans 1929–1933

  3. Kelland L (2007) Nat Rev Cancer 7:573–584

    Article  CAS  PubMed  Google Scholar 

  4. Ott I, Gust R (2007) Arch Pharm (Weinheim) 340:117–126

    Article  CAS  Google Scholar 

  5. Ang WH, Dyson PJ (2006) Eur J Inorg Chem 20:4003–4018

    Google Scholar 

  6. Reedijk J (2009) Eur J Inorg Chem 1303–1312

  7. Clarke MJ (2003) Coord Chem Rev 236:209–233

    Article  CAS  Google Scholar 

  8. Wang D, Lippard SJ (2005) Nat Rev Drug Discov 4:307–320

    Article  CAS  PubMed  Google Scholar 

  9. Bosch ME, Sanchez AJ, Rojas FS, Ojeda CB (2008) J Pharm Biomed Anal 47:451–459

    Article  CAS  PubMed  Google Scholar 

  10. Nordhoff E, Kirpekar F, Roepstorff P (1996) Mass Spectrom Rev 15:67–138

    Article  Google Scholar 

  11. Hadjiliadis N, Sletten E (eds) (2009) Metal complex–DNA interactions. Blackwell, Oxford

  12. Iannitti-Tito P, Weimann A, Wickham G, Sheil MM (2000) Analyst 125:33–627

    Article  Google Scholar 

  13. Beck JL, Colgrave ML, Ralph SF, Sheil MM (2001) Mass Spectrom Rev 20:61–87

    Article  CAS  PubMed  Google Scholar 

  14. Gupta R, Kapur A, Beck JL, Sheil MM (2001) Rapid Commun Mass Spectrom 15:2472–2480

    Article  CAS  PubMed  Google Scholar 

  15. Rosu F, Pirotte S, De Pauw E, Gabelica V (2006) Int J Mass Spectrom 253:156–171

    Article  CAS  Google Scholar 

  16. Egger AE, Hartinger CG, Ben Hamidane H, Tsybin YO, Keppler BK, Dyson PJ (2008) Inorg Chem 47:10626–10633

    Article  CAS  PubMed  Google Scholar 

  17. Nyakas A, Eymann M, Schurch S (2009) J Am Soc Mass Spectrom 20:792–804

    Article  CAS  PubMed  Google Scholar 

  18. Fichtinger-Schepman AM, van der Veer JL, den Hartog JH, Lohman PH, Reedijk J (1985) Biochemistry 24:707–713

    Article  CAS  PubMed  Google Scholar 

  19. Heringova P, Woods J, Mackay FS, Kasparkova J, Sadler PJ, Brabec V (2006) J Med Chem 49:7792–7798

    Article  CAS  PubMed  Google Scholar 

  20. Wynne P, Newton C, Ledermann JA, Olaitan A, Mould TA, Hartley JA (2007) Br J Cancer 97:927–933

    CAS  PubMed  Google Scholar 

  21. Pizarro AM, Sadler PJ (2009) Biochimie 91:1198–1211

    Google Scholar 

  22. Ni J, Pomerantz C, Rozenski J, Zhang Y, McCloskey JA (1996) Anal Chem 68:1989–1999

    Article  CAS  PubMed  Google Scholar 

  23. Mestroni G, Alessio E, Sava G (1998) Patent no. WO 98/00431, Italy

  24. Scolaro C, Bergamo A, Brescacin L, Delfino R, Cocchietto M, Laurenczy G, Geldbach TJ, Sava G, Dyson PJ (2005) J Med Chem 48:4161–4171

    Article  CAS  PubMed  Google Scholar 

  25. Lipponer KG, Vogel E, Keppler BK (1996) Met Based Drugs 3:243–260

    Article  CAS  PubMed  Google Scholar 

  26. Lecchi P, Pannell LK (1995) J Am Soc Mass Spectrom 6:972–975

    Article  CAS  Google Scholar 

  27. Kirpekar F, Berkenkamp S, Hillenkamp F (1999) Anal Chem 71:2334–2339

    Article  CAS  PubMed  Google Scholar 

  28. Ang WH, Daldini E, Scolaro C, Scopelliti R, Juillerat-Jeannerat L, Dyson PJ (2006) Inorg Chem 45:9006–9013

    Article  CAS  PubMed  Google Scholar 

  29. Zhang LK, Gross ML (2000) J Am Soc Mass Spectrom 11:854–865

    Article  CAS  PubMed  Google Scholar 

  30. Lecchi P, Le HMT, Pannell LK (1995) Nucleic Acids Res 23:1276–1277

    Article  CAS  PubMed  Google Scholar 

  31. Taranenko NI, Chung CN, Zhu YF, Allman SL, Golovlev VV, Isola NR, Martin SA, Haff LA, Chen CH (1997) Rapid Commun Mass Spectrom 11:386–392

    Article  CAS  PubMed  Google Scholar 

  32. Todd RC, Lippard SJ (2009) Metallomics 1:280–291

    Article  CAS  PubMed  Google Scholar 

  33. Reed E (2001) In: Chabner BC, Longo DL (eds) Cancer chemotherapy and biotherapy. Lippincott Williams & Wilkins, Philadelphia, pp 332–343

    Google Scholar 

  34. Bregadze VG (1996) In: Sigel A, Sigel H (eds) Metal ions in biological systems. Dekker, New York, pp 419–451

    Google Scholar 

  35. Dorcier A, Hartinger CG, Scopelliti R, Fish RH, Keppler BK, Dyson PJ (2008) J Inorg Biochem 102:1066–1076

    Article  CAS  PubMed  Google Scholar 

  36. Scolaro C, Chaplin AB, Hartinger CG, Bergamo A, Cocchietto M, Keppler BK, Sava G, Dyson PJ (2007) Dalton Trans 5065–5072

  37. Morbidelli L, Donnini S, Filippi S, Messori L, Piccioli F, Orioli P, Sava G, Ziche M (2003) Br J Cancer 88:1484–1491

    Article  CAS  PubMed  Google Scholar 

  38. Bergamo A, Masi A, Dyson PJ, Sava G (2008) Int J Oncol 33:1281–1289

    CAS  PubMed  Google Scholar 

  39. Groessl M, Hartinger CG, Dyson PJ, Keppler BK (2008) J Inorg Biochem 102:1060–1065

    Article  CAS  PubMed  Google Scholar 

  40. Groessl M, Reisner E, Hartinger CG, Eichinger R, Semenova O, Timerbaev AR, Jakupec MA, Arion VB, Keppler BK (2007) J Med Chem 50:2185–2193

    Article  CAS  PubMed  Google Scholar 

  41. Dorcier A, Ang WH, Bolano S, Gonsalvi L, Juillerat-Jeannerat L, Laurenczy G, Peruzzini M, Phillips AD, Zanobini F, Dyson PJ (2006) Organometallics 25:4090–4096

    Article  CAS  Google Scholar 

  42. Dorcier A, Dyson PJ, Gossens C, Rothlisberger U, Scopelliti R, Tavernelli I (2005) Organometallics 24:2114–2123

    Article  CAS  Google Scholar 

  43. Casini A, Mastrobuoni G, Terenghi M, Gabbiani C, Monzani E, Moneti G, Casella L, Messori L (2007) J Biol Inorg Chem 12:1107–1117

    Article  CAS  PubMed  Google Scholar 

  44. McLuckey SA, Vanberkel GJ, Glish GL (1992) J Am Soc Mass Spectrom 3:60–70

    Article  CAS  Google Scholar 

  45. de Hoffmann E (2007) Mass spectrometry: principles and applications. Wiley, Chichester

    Google Scholar 

  46. Blommaert FA, Van Dick-Knijnenburg HCM, Dijt FJ, Denengelse L, Baan RA, Berends F, Fichtinger-Schepman AMJ (1995) Biochemistry 34:8474–8480

    Article  CAS  PubMed  Google Scholar 

  47. Kasparkova J, Vojtiskova M, Natile G, Brabec V (2008) Chem Eur J 14:1330–1341

    Article  CAS  Google Scholar 

  48. Malina J, Novakova O, Keppler BK, Alessio E, Brabec V (2001) J Biol Inorg Chem 6:435–445

    Article  CAS  PubMed  Google Scholar 

  49. Zorbas-Seifried S, Hartinger CG, Meelich K, Galanski M, Keppler BK, Zorbas H (2006) Biochemistry 45:14817–14825

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Laure Menin for guidance in operating the quadrupole TOF instrument. M.G. thanks the Austrian Science Foundation for financial support (Schrödinger Fellowship J2882-N19).

Author information

Authors and Affiliations

  1. Institut des Sciences et Ingénierie Chimiques, École Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland

    Michael Groessl, Yury O. Tsybin & Paul J. Dyson

  2. Institute of Inorganic Chemistry, University of Vienna, Währinger Str. 42, Vienna, 1090, Austria

    Christian G. Hartinger & Bernhard K. Keppler

Authors
  1. Michael Groessl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yury O. Tsybin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christian G. Hartinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bernhard K. Keppler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Paul J. Dyson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael Groessl.

Electronic supplementary material

Supporting information containing MALDI-MS data for the analysis of the double strands as well as ESI-MS and CID mass spectra for determining metallodrug–oligonucleotide interactions is provided.

Supplementary material 1 (PDF 1.63 mb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Groessl, M., Tsybin, Y.O., Hartinger, C.G. et al. Ruthenium versus platinum: interactions of anticancer metallodrugs with duplex oligonucleotides characterised by electrospray ionisation mass spectrometry. J Biol Inorg Chem 15, 677–688 (2010). https://doi.org/10.1007/s00775-010-0635-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00775-010-0635-0

Keywords

Search

Navigation