Display options
Cite
Koeller KJ, Harris GD, Aston K, et al. DNA Binding Polyamides and the Importance of DNA Recognition in their use as Gene-Specific and Antiviral Agents. Med Chem (Los Angeles). 2014;4:338-344doi: 10.4172/2161-0444.1000162.
Koeller, K. J., Harris, G. D., Aston, K., He, G., Castaneda, C. H., Thornton, M. A., Edwards, T. G., Wang, S., Nanjunda, R., Wilson, W. D., Fisher, C., & Bashkin, J. K. (2014). DNA Binding Polyamides and the Importance of DNA Recognition in their use as Gene-Specific and Antiviral Agents. Medicinal chemistry, 4338-344. https://doi.org/10.4172/2161-0444.1000162
Koeller, Kevin J, et al. "DNA Binding Polyamides and the Importance of DNA Recognition in their use as Gene-Specific and Antiviral Agents." Medicinal chemistry vol. 4 (2014): 338-344. doi: https://doi.org/10.4172/2161-0444.1000162
Koeller KJ, Harris GD, Aston K, He G, Castaneda CH, Thornton MA, Edwards TG, Wang S, Nanjunda R, Wilson WD, Fisher C, Bashkin JK. DNA Binding Polyamides and the Importance of DNA Recognition in their use as Gene-Specific and Antiviral Agents. Med Chem (Los Angeles). 2014 Feb 20;4:338-344. doi: 10.4172/2161-0444.1000162. PMID: 24839583; PMCID: PMC4022477.
Copy Download .nbib Format: NLM
Share it on

Med Chem (Los Angeles). 2014 Feb 20;4:338-344. doi: 10.4172/2161-0444.1000162.

DNA Binding Polyamides and the Importance of DNA Recognition in their use as Gene-Specific and Antiviral Agents.

Medicinal chemistry

Kevin J Koeller, G Davis Harris, Karl Aston, Gaofei He, Carlos H Castaneda, Melissa A Thornton, Terri G Edwards, Shuo Wang, Rupesh Nanjunda, W David Wilson, Chris Fisher, James K Bashkin

Affiliations

  1. Department of Chemistry & Biochemistry, University of Missouri-St. Louis, St.Louis, MO 63121, USA.
  2. NanoVir, LLC, Kalamazoo, MI 49008, USA.
  3. Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA.
  4. Department of Chemistry & Biochemistry, University of Missouri-St. Louis, St.Louis, MO 63121, USA ; NanoVir, LLC, Kalamazoo, MI 49008, USA.

PMID: 24839583 PMCID: PMC4022477 DOI: 10.4172/2161-0444.1000162

Abstract

There is a long history for the bioorganic and biomedical use of N-methyl-pyrrole-derived polyamides (PAs) that are higher homologs of natural products such as distamycin A and netropsin. This work has been pursued by many groups, with the Dervan and Sugiyama groups responsible for many breakthroughs. We have studied PAs since about 1999, partly in industry and partly in academia. Early in this program, we reported methods to control cellular uptake of polyamides in cancer cell lines and other cells likely to have multidrug resistance efflux pumps induced. We went on to discover antiviral polyamides active against HPV31, where SAR showed that a minimum binding size of about 10 bp of DNA was necessary for activity. Subsequently we discovered polyamides active against two additional high-risk HPVs, HPV16 and 18, a subset of which showed broad spectrum activity against HPV16, 18 and 31. Aspects of our results presented here are incompatible with reported DNA recognition rules. For example, molecules with the same cognate DNA recognition properties varied from active to inactive against HPVs. We have since pursued the mechanism of action of antiviral polyamides, and polyamides in general, with collaborators at NanoVir, the University of Missouri-St. Louis, and Georgia State University. We describe dramatic consequences of β-alanine positioning even in relatively small, 8-ring polyamides; these results contrast sharply with prior reports. This paper was originally presented by JKB as a Keynote Lecture in the 2

References

  1. Biochemistry. 1999 Feb 16;38(7):2143-51 - PubMed
  2. Chemistry. 2014 Jan 27;20(5):1310-7 - PubMed
  3. Cancer Sci. 2011 Dec;102(12):2221-30 - PubMed
  4. Org Lett. 2011 Oct 21;13(20):5612-5 - PubMed
  5. Nucleic Acids Res. 2008 May;36(9):2889-94 - PubMed
  6. Nucleic Acids Res. 2002 Apr 15;30(8):1834-41 - PubMed
  7. J Am Chem Soc. 2002 Mar 13;124(10):2153-63 - PubMed
  8. Bioorg Med Chem Lett. 2006 Jul 15;16(14):3745-50 - PubMed
  9. Biochemistry. 2003 Jun 10;42(22):6891-903 - PubMed
  10. J Am Chem Soc. 2006 Jul 12;128(27):8766-76 - PubMed
  11. Nucleic Acids Res. 2009 Sep;37(16):5550-8 - PubMed
  12. Mol Pharmacol. 1998 Aug;54(2):280-90 - PubMed
  13. Anal Biochem. 2012 Apr 1;423(1):178-83 - PubMed
  14. Antiviral Res. 2011 Aug;91(2):177-86 - PubMed
  15. Mol Cell. 2000 Nov;6(5):1013-24 - PubMed
  16. Bioorg Med Chem Lett. 2003 May 5;13(9):1565-70 - PubMed
  17. PLoS One. 2013 Oct 02;8(10):e75406 - PubMed
  18. Chem Biol. 1996 May;3(5):369-77 - PubMed
  19. Biopolymers. 2013 Aug;99(8):497-507 - PubMed
  20. Biochemistry. 2012 Dec 11;51(49):9796-806 - PubMed
  21. Infect Agents Dis. 1993 Apr;2(2):74-86 - PubMed
  22. Semin Cancer Biol. 1999 Dec;9(6):379-86 - PubMed
  23. J Am Chem Soc. 2006 Nov 22;128(46):14905-12 - PubMed
  24. Bioorg Med Chem. 2001 Jan;9(1):7-17 - PubMed
  25. Nat Struct Biol. 1998 Feb;5(2):104-9 - PubMed
  26. Nucleic Acids Res. 2011 May;39(10):4265-74 - PubMed
  27. Otolaryngol Head Neck Surg. 1991 Mar;104(3):303-10 - PubMed
  28. Nucleic Acids Symp Ser. 1999;(42):249-50 - PubMed
  29. Proc Natl Acad Sci U S A. 2012 Jan 24;109(4):1023-8 - PubMed
  30. Bioorg Med Chem. 2008 Feb 15;16(4):2093-102 - PubMed
  31. Biochemistry. 1996 Sep 24;35(38):12532-7 - PubMed
  32. Mol Biosyst. 2005 Oct;1(4):307-17 - PubMed
  33. Chembiochem. 2012 Jun 18;13(9):1366-74 - PubMed
  34. EMBO J. 2001 Jun 15;20(12):3218-28 - PubMed
  35. Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10389-92 - PubMed
  36. Chem Biol. 1997 Aug;4(8):569-78 - PubMed
  37. J Org Chem. 2013 Jan 4;78(1):124-33 - PubMed
  38. J Virol. 2013 Apr;87(7):3979-89 - PubMed
  39. Bioorg Med Chem. 2010 Jan 15;18(2):978-83 - PubMed
  40. Bioorg Med Chem. 2013 Sep 1;21(17):5436-41 - PubMed
  41. J Med Virol. 1992 May;37(1):22-9 - PubMed
  42. Biotechniques. 2000 Nov;29(5):1034-6, 1038, 1040-1 - PubMed
  43. Nature. 1998 Jan 29;391(6666):468-71 - PubMed
  44. Chemistry. 2002 Oct 18;8(20):4781-90 - PubMed
  45. Mol Cell. 2000 Nov;6(5):999-1011 - PubMed
  46. Bioorg Med Chem. 2007 Nov 15;15(22):6927-36 - PubMed
  47. J Biomol Tech. 2006 Apr;17(2):103-13 - PubMed
  48. Gynecol Oncol. 1991 Sep;42(3):250-5 - PubMed
  49. J Am Chem Soc. 2004 Mar 24;126(11):3406-7 - PubMed
  50. Bioorg Med Chem. 2013 Oct 15;21(20):6101-14 - PubMed
  51. Biochimie. 2014 Jul;102:83-91 - PubMed
  52. Chem Commun (Camb). 2013 Oct 4;49(76):8543-5 - PubMed
  53. Electrophoresis. 2001 Jun;22(10):1979-86 - PubMed
  54. Anal Biochem. 2013 Aug 15;439(2):99-101 - PubMed
  55. Bioorg Med Chem. 2012 Jan 15;20(2):693-701 - PubMed
  56. Biochimie. 2013 Feb;95(2):271-9 - PubMed
  57. Curr Opin Chem Biol. 1999 Dec;3(6):688-93 - PubMed
  58. Virology. 2002 Sep 30;301(2):334-41 - PubMed
  59. Biochemistry. 1990 Jul 3;29(26):6139-45 - PubMed
  60. Nucleic Acids Res. 2008 Jun;36(11):e63 - PubMed
  61. Anal Biochem. 1996 Dec 1;243(1):198-201 - PubMed
  62. J Org Chem. 2000 Sep 8;65(18):5506-13 - PubMed
  63. Methods Mol Biol. 2009;543:37-47 - PubMed
  64. J Med Chem. 2009 Aug 13;52(15):4604-12 - PubMed
  65. Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4343-8 - PubMed
  66. J Am Chem Soc. 2013 Nov 6;135(44):16468-77 - PubMed
  67. J Mol Biol. 2002 Jun 28;320(1):55-71 - PubMed

Publication Types

Grant support