Get access

Strand Invasion of DNA Quadruplexes by PNA: Comparison of Homologous and Complementary Hybridization

Authors

  • Dr. Anisha Gupta,

    1. Department of Chemistry and Center for Nucleic Acids Science and Technology, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213 (USA)
    Search for more papers by this author
  • Ling-Ling Lee,

    1. Department of Chemistry and Center for Nucleic Acids Science and Technology, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213 (USA)
    Search for more papers by this author
  • Dr. Subhadeep Roy,

    1. Department of Chemistry and Center for Nucleic Acids Science and Technology, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213 (USA)
    Search for more papers by this author
  • Farial A. Tanious,

    1. Department of Chemistry, Georgia State University, P.O. Box 3965, Atlanta, GA 30303-3965
    Search for more papers by this author
  • Dr. W. David Wilson,

    1. Department of Chemistry, Georgia State University, P.O. Box 3965, Atlanta, GA 30303-3965
    Search for more papers by this author
  • Dr. Danith H. Ly,

    1. Department of Chemistry and Center for Nucleic Acids Science and Technology, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213 (USA)
    Search for more papers by this author
  • Dr. Bruce A. Armitage

    Corresponding author
    1. Department of Chemistry and Center for Nucleic Acids Science and Technology, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213 (USA)
    • Department of Chemistry and Center for Nucleic Acids Science and Technology, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213 (USA)
    Search for more papers by this author

Abstract

Molecular recognition of DNA quadruplex structures is envisioned to be a strategy for regulating gene expression at the transcriptional level and for in situ analysis of telomere structure and function. The recognition of DNA quadruplexes by peptide nucleic acid (PNA) oligomers is presented here, with a focus on comparing complementary, heteroduplex-forming and homologous, heteroquadruplex-forming PNAs. Surface plasmon resonance and optical spectroscopy experiments demonstrated that the efficacy of a recognition mode depended strongly on the target. Homologous PNA readily invades a quadruplex derived from the promoter regulatory region found upstream of the MYC proto-oncogene to form a heteroquadruplex at high potassium concentration mimicking the intracellular environment, whereas complementary PNA exhibits virtually no hybridization. In contrast, complementary PNA is superior to the homologous in hybridizing to a quadruplex modeled on the human telomere sequence. The results are discussed in terms of the different structural morphologies of the quadruplex targets and the implications for in vivo recognition of quadruplexes by PNAs.

Ancillary