title: Strand invasion of DNA quadruplexes by PNA: comparison of homologous and complementary hybridization.
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.
authors.affiliation: Department of Chemistry and Center for Nucleic Acids Science and Technology, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213, USA.
authors.forename: Anisha
authors.initials: A
authors.lastname: Gupta
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Lee
authors.forename: Subhadeep
authors.initials: S
authors.lastname: Roy
authors.forename: Farial A
authors.initials: FA
authors.lastname: Tanious
authors.forename: W David
authors.initials: WD
authors.lastname: Wilson
authors.forename: Danith H
authors.initials: DH
authors.lastname: Ly
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Armitage
mesh_terms: D001665:Binding Sites; D002232:Carbocyanines / Q000737:chemistry; D002942:Circular Dichroism; D018076:DNA, Complementary; D054856:G-Quadruplexes; D006801:Humans; D015394:Molecular Structure; D009693:Nucleic Acid Hybridization; D020135:Peptide Nucleic Acids / Q000737:chemistry*; D000090063:Proto-Oncogene Mas; D012689:Sequence Homology, Nucleic Acid
chemical_list: D002232:Carbocyanines; D018076:DNA, Complementary; C000715470:MAS1 protein, human; D020135:Peptide Nucleic Acids; D000090063:Proto-Oncogene Mas; C000657:cyanine dye 1
keywords: DNA; duplexes; oligomers; peptide nucleic acids; quadruplexes