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Supramolecular Self-Assembling Cyanine as an Alternative to Ethidium Bromide Displacement in DNA-Drug Model Interactions during High Throughput Screening

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Abstract

Supramolecular self-assembling cyanine and spermine binding to genomic DNA was a model for DNA–drug interactions during high throughput screening. Spermine competitively inhibited the self-assembly of cyanine upon DNA scaffolds as signaled by decreased fluorescence from the DNA–cyanine J-aggregate. The sequence of DNA exposure to cyanine or spermine was critical in determining the magnitude of inhibition. Methanol potentiated spermine inhibition by >10-fold. The IC50 and association constant (Ka) in 16% methanol were 0.35 ± 0.03 μM and 2.86 × 106 M–1 respectively, relative to 3.97 ± 0.47 μM and 0.25 × 106 M–1 respectively, in buffer. Increasing concentrations of cyanine overcame spermine inhibition, demonstrating the reversibility of DNA–drug interactions. λDNA interacted similarly with spermine and cyanine, confirming system flexibility. The model drug, dye and methanol effects are discussed in detail. Cyanine might be a safer alternative to the mutagenic ethidium bromide for investigating DNA–drug interactions.

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References

  1. T. Kodadek, Trends Biochem. Sci., 1998, 23, 79.

    Article  CAS  PubMed  Google Scholar 

  2. R. Palchaudhuri and P. U. Hergenrother, Curr. Opin. Biotechnol., 2007, 18, 497.

    Article  CAS  PubMed  Google Scholar 

  3. A. Erdem and M. Ozsoz, Electroanalysis, 2002, 14, 965.

    Article  CAS  Google Scholar 

  4. I. Haq and J. Ladbury, J. Mol. Recognit., 2000, 13, 188.

    Article  CAS  PubMed  Google Scholar 

  5. K. E. Achyuthan and D. G. Whitten, Comb. Chem. High Throughput Screening, 2007, 10, 399.

    Article  CAS  Google Scholar 

  6. W. C. Tse and D. L. Boger, Acc. Chem. Res., 2004, 37, 61.

    Article  CAS  PubMed  Google Scholar 

  7. K. E. Achyuthan, J. L. McClain, Z. Zhou, D. G. Whitten, and D. W. Branch, Anal. Sci., 2009, 25, 469.

    Article  CAS  PubMed  Google Scholar 

  8. Q. Huang and W.-L. Fu, Clin. Chem. Lab. Med., 2005, 43, 841.

    Article  CAS  PubMed  Google Scholar 

  9. S. Venkiteswaran, T. Thomas, and T. J. Thomas, in “Polyamine Cell Signaling: Physiology, Pharmacology and Cancer Research”, 2006, Humana Press, Totowa, NJ, 91.

  10. M. Wang, G. L. Silva, and B. A. Armitage, J. Am. Chem. Soc., 2000, 122, 9977.

    Article  CAS  Google Scholar 

  11. V. Vijayanathan, T. Thomas, A. Shirahata, and T. J. Thomas, Biochemistry, 2001, 40, 13644.

    Article  CAS  PubMed  Google Scholar 

  12. J. Szekely and K. S. Gates, Chem. Res. Toxicol., 2006, 19, 117.

    Article  CAS  PubMed  Google Scholar 

  13. H.-F. Wang, R. Shen, and N. Tang, Eur. J. Med. Chem., 2009, 44, 4509.

    Article  CAS  PubMed  Google Scholar 

  14. R. Shen, P. Wang, and N. Tang, J. Fluoresc., 2009, 19, 1073.

    Article  CAS  PubMed  Google Scholar 

  15. V. L. Singer, T. E. Lawlor, and S. Yue, Mutat. Res., 1999, 439, 37.

    Article  CAS  PubMed  Google Scholar 

  16. B. P. Matselyukh, S. M. Yarmoluk, A. B. Matselyukh, V. B. Kovalska, I. O. Kocheshev, D. V. Kryvorotenko, and S. S. Lukashov, J. Biochem. Biophys. Methods, 2003, 57, 35.

    Article  CAS  PubMed  Google Scholar 

  17. H. Tian and F. Meng, “Cyanine Dyes for Solar Cells and Optical Data Storage”, ed. S.-H. Kim, 2006, Chap. 2, Elsevier, St. Louis, MO, 47.

  18. E. N. Timofeev, V. E. Kuznetsova, A. S. Zasedatelev, and A. V. Chudinov, Lett. Org. Chem., 2009, 6, 71.

    Article  CAS  Google Scholar 

  19. A. Furstenberg, T. G. Deligeorgiev, N. I. Gadjev, A. A. Vasilev, and E. Vauthey, Chem. Eur. J., 2007, 13, 8600.

    Article  PubMed  Google Scholar 

  20. J. Pelta, F. Livolant, and J.-L. Sikorav, J. Biol. Chem., 1996, 271, 5656.

    Article  CAS  PubMed  Google Scholar 

  21. A. A. Ouameur and H.-A. Tajmir-Riahi, J. Biol. Chem., 2004, 279, 42041.

    Article  CAS  PubMed  Google Scholar 

  22. B. C. Baguley, W. A. Denny, G. J. Atwell, and B. F. Cain, J. Med. Chem., 1981, 24, 170.

    Article  CAS  PubMed  Google Scholar 

  23. A. J. Geall, M. A. W. Eaton, T. Baker, C. Catterall, and I. S. Blagbrough, FEBS Lett., 1999, 459, 337.

    Article  CAS  PubMed  Google Scholar 

  24. A. J. Geall and I. S. Blagbrough, J. Pharm. Biomed. Anal., 2000, 22, 849.

    Article  CAS  PubMed  Google Scholar 

  25. T. Biver, A. De Biasi, F. Secco, M. Venturini, and S. Yarmoluk, Biophys. J., 2005, 89, 374.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. D. Porschke, Biochemistry, 1984, 23, 4821.

    Article  CAS  PubMed  Google Scholar 

  27. T. Antony, T. Thomas, A. Shirahata, and T. J. Thomas, Biochemistry, 1999, 38, 10775.

    Article  CAS  PubMed  Google Scholar 

  28. A. R. Morgan, J. S. Lee, D. E. Pulleyblank, N. L. Murray and D. H. Evans, Nucleic Acids Res., 1979, 7, 547.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. V. Pavlov, P. K. Thoo Lin, and V. Rodilla, Chem.-Biol. Interact., 2001, 137, 15.

    Article  CAS  PubMed  Google Scholar 

  30. H. S. Basu, M. Pellarin, B. G. Feuerstein, A. Shirahata, K. Samejima, D. F. Deen, and L. J. Marton, Cancer Res., 1993, 53, 3948.

    CAS  PubMed  Google Scholar 

  31. E. Rowatt and R. J. P. Williams, J. Inorg. Biochem., 1992, 46, 87.

    Article  CAS  PubMed  Google Scholar 

  32. V. A. Bloomfield, Biopolymer., 1997, 44, 269.

    Article  CAS  Google Scholar 

  33. M. Matzeu, G. Onori, and A. Santucci, Colloids Surf., B, 1999, 13, 157.

    Article  CAS  Google Scholar 

  34. D. J. Hill and J. S. Moore, Proc. Natl. Acad. Sci. U. S. A., 2002, 99, 5053.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Biosensors and Nanomaterials Department, Sandia National Laboratories, Albuquerque, NM, USA

    Komandoor E. Achyuthan & Darren W. Branch

  2. Department of Chemical and Nuclear Engineering, University of New Mexico, Albuquerque, NM, USA

    David G. Whitten

Authors
  1. Komandoor E. Achyuthan
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  2. David G. Whitten
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  3. Darren W. Branch
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Correspondence to Komandoor E. Achyuthan.

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Achyuthan, K.E., Whitten, D.G. & Branch, D.W. Supramolecular Self-Assembling Cyanine as an Alternative to Ethidium Bromide Displacement in DNA-Drug Model Interactions during High Throughput Screening. ANAL. SCI. 26, 55–61 (2010). https://doi.org/10.2116/analsci.26.55

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  • DOI: https://doi.org/10.2116/analsci.26.55

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