Kinetic discrimination in recognition of DNA quadruplex targets by guanine-rich heteroquadruplex-forming PNA probes.

Department of Chemistry and Center for Nucleic Acids Science and Technology, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213, USA.
Chemical Communications (Impact Factor: 6.38). 06/2011; 47(30):8524-6. DOI:10.1039/c1cc12805a
Source: PubMed

ABSTRACT Guanine-rich peptide nucleic acid probes hybridize to DNA G quadruplex targets with high affinity, forming PNA-DNA heteroquadruplexes. We report a surprising degree of kinetic discrimination for PNA heteroquadruplex formation with a series of DNA targets. The fastest hybridization is observed for targets folded into parallel morphologies.

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    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.
    ChemBioChem 07/2013; · 3.74 Impact Factor


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Subhadeep Roy