Skip to main content
SpringerLink
Log in

The sequence selectivity of DNA-targeted 9-aminoacridine cisplatin analogues in a telomere-containing DNA sequence

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

Abstract

In this study, the detailed DNA sequence specificity of four acridine Pt complexes was examined and compared with that of cisplatin. The DNA sequence specificity was determined in a telomere-containing DNA sequence using a polymerase stop assay, with a fluorescent primer and an automated capillary DNA sequencer. The Pt compounds included an acridine intercalating moiety that was modified to give a 9-aminoacridine derivative, a 7-methoxy-9-aminoacridine derivative, a 7-fluoro-9-aminoacridine derivative and a 9-ethanolamine-acridine derivative. Compared with cisplatin, the DNA sequence specificity was most altered for the 7-methoxy-9-aminoacridine compound, followed by the 9-aminoacridine derivative, the 7-fluoro-9-aminoacridine compound and the 9-ethanolamine-acridine derivative. The DNA sequence selectivity for the four acridine Pt complexes was shifted away from runs of consecutive guanines towards single guanine bases, especially 5′-GA dinucleotides and sequences that contained 5′-CG. The sequence specificity was examined in telomeric and non-telomeric DNA sequences. Although it was found that telomeric DNA sequences were extensively damaged by the four acridine Pt complexes, there was no extra preference for telomeric sequences.

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

Similar content being viewed by others

Abbreviations

9AmAcPtCl2 :

Dichlorido(N-2-[(2-aminoethyl)amino]-ethyl)-9-aminoacridine-4-carboxamide)platinum(II)

7-Methoxy-9AmAcPtCl2 :

Dichlorido(N-2-[(2-aminoethyl)amino]-ethyl)-7-methoxy-9-aminoacridine-4-carboxamide)platinum(II)

7-Fluoro-9AmAcPtCl2 :

Dichlorido(N-2-[(2-aminoethyl)amino]-ethyl)-7-fluoro-9-aminoacridine-4-carboxamide)platinum(II)

9-Ethanolamine-AcPtCl2 :

Dichlorido(N-2-[(2-aminoethyl)amino]-ethyl)-9-ethanolamine-acridine-4-carboxamide)platinum(II)

CE-LIF:

Capillary electrophoresis with laser-induced-fluorescence detection

Cisplatin:

cis-Diamminedichloridoplatinum(II)

DMF:

Dimethylformamide

Tris:

Tris(hydroxymethyl)aminomethane

References

  1. Loehrer PJ, Einhorn LH (1984) Ann Intern Med 100:704–713

    PubMed  CAS  Google Scholar 

  2. Kelland LR (2007) Nat Rev Cancer 7:573–584

    Article  PubMed  CAS  Google Scholar 

  3. Bruhn SL, Pil PM, Essigmann JM, Housman DE, Lippard SJ (1992) Proc Natl Acad Sci USA 89:2307–2311

    Article  PubMed  CAS  Google Scholar 

  4. Jamieson ER, Lippard SJ (1999) Chem Rev 99:2467–2498

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. Jung YW, Lippard SJ (2007) Chem Rev 107:1387–1407

    Article  PubMed  CAS  Google Scholar 

  8. Ponti M, Forrow SM, Souhami RL, D’Incalci M, Hartley JA (1991) Nucleic Acids Res 19:2929–2933

    Article  PubMed  CAS  Google Scholar 

  9. Murray V, Motyka H, England PR, Wickham G, Lee HH, Denny WA, McFadyen WD (1992) J Biol Chem 267:18805–18809

    PubMed  CAS  Google Scholar 

  10. Murray V (2000) Prog Nucleic Acid Res Mol Biol 63:367–415

    Article  CAS  Google Scholar 

  11. Denny WA (1989) Anticancer Drug Des 4:241–263

    PubMed  CAS  Google Scholar 

  12. Whittaker JK, McFadyen WD, Wickham G, Wakelin LPG, Murray V (1998) Nucleic Acids Res 26:3933–3939

    Article  PubMed  CAS  Google Scholar 

  13. Temple MD, McFadyen WD, Holmes RJ, Denny WA, Murray V (2000) Biochemistry 39:5593–5599

    Article  PubMed  CAS  Google Scholar 

  14. Carland M, Grannas MJ, Cairns MJ, Roknic VJ, Denny WA, McFadyen WD, Murray V (2010) J Inorg Biochem 104:815–819

    Google Scholar 

  15. Whittaker JK, McFadyen WD, Baguley BC, Murray V (2001) Anticancer Drug Des 16:81–89

    PubMed  CAS  Google Scholar 

  16. Temple MD, Recabarren P, McFadyen WD, Holmes RJ, Denny WA, Murray V (2002) Biochim Biophys Acta 1574:223–230

    PubMed  CAS  Google Scholar 

  17. Lee HH, Palmer BD, Baguley BC, Chin M, McFadyen WD, Wickham G, Thorsbourne-Palmer D, Wakelin LPG, Denny WA (1992) J Med Chem 35:2983–2987

    Article  PubMed  CAS  Google Scholar 

  18. Holmes RJ, McKeage MJ, Murray V, Denny WA, McFadyen WD (2001) J Inorg Biochem 85:209–217

    Article  PubMed  CAS  Google Scholar 

  19. Murray V (1989) Nucl Acids Res 17:8889

    Article  PubMed  CAS  Google Scholar 

  20. Paul M, Murray V (2011) Biomed Chromatogr (in press)

  21. Viscardi V, Clerici M, Cartagena-Lirola H, Longhese MP (2005) Biochimie 87:613–624

    Article  PubMed  CAS  Google Scholar 

  22. Henderson ER, Blackburn EH (1989) Mol Cell Biol 9:345–348

    PubMed  CAS  Google Scholar 

  23. Cesare AJ, Reddel RR (2010) Nat Rev Genet 11:319–330

    Article  PubMed  CAS  Google Scholar 

  24. Moyzis RK, Buckingham JM, Cram LS, Dani M, Deaven LL, Jones MD, Meyne J, Ratliff RL, Wu JR (1988) Proc Natl Acad Sci USA 85:6622–6626

    Article  PubMed  CAS  Google Scholar 

  25. Wright WE, Tesmer VM, Huffman KE, Levene SD, Shay JW (1997) Genes Dev 11:2801–2809

    Article  PubMed  CAS  Google Scholar 

  26. Griffith JD, Comeau L, Rosenfield S, Stansel RM, Bianchi A, Moss H, de Lange T (1999) Cell 97:503–514

    Article  PubMed  CAS  Google Scholar 

  27. Yu HQ, Miyoshi D, Sugimoto N (2006) J Am Chem Soc 128:15461–15468

    Article  PubMed  CAS  Google Scholar 

  28. Burge S, Parkinson GN, Hazel P, Todd AK, Neidle S (2006) Nucleic Acids Res 34:5402–5415

    Article  PubMed  CAS  Google Scholar 

  29. Nelson SM, Ferguson LR, Denny WA (2004) Cell Chromosome 3:2–27

    Article  PubMed  Google Scholar 

  30. Reed JE, Neidle S, Vilar R (2007) Chem Commun 42:4366–4368

    Google Scholar 

  31. Burstyn JN, Heiger-Bernays WJ, Cohen SM, Lippard SJ (2000) Nucleic Acids Res 28:4237–4243

    Article  PubMed  CAS  Google Scholar 

  32. Brabec V (2002) Prog Nucleic Acid Res Mol Biol 71:1–68

    Article  PubMed  CAS  Google Scholar 

  33. Adams A, Guss M, Collyer C, Denny WA, Wakelin LPG (1999) Biochemistry 38:9221–9233

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

Support of this work by the University of New South Wales Science Faculty Research Grant Scheme is gratefully acknowledged.

Author information

Authors and Affiliations

  1. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, 2052, Australia

    Moumita Paul & Vincent Murray

Authors
  1. Moumita Paul
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vincent Murray
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vincent Murray.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Paul, M., Murray, V. The sequence selectivity of DNA-targeted 9-aminoacridine cisplatin analogues in a telomere-containing DNA sequence. J Biol Inorg Chem 16, 735–743 (2011). https://doi.org/10.1007/s00775-011-0774-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00775-011-0774-y

Keywords

Search

Navigation