Loop and backbone modifications of peptide nucleic acid improve g-quadruplex binding selectivity. Lusvarghi, S., Murphy, C. T, Roy, S., Tanious, F. A, Sacui, I., Wilson, W D., Ly, D. H, & Armitage, B. A Journal of the American Chemical Society, 2009.
Loop and backbone modifications of peptide nucleic acid improve g-quadruplex binding selectivity [link]Paper  doi  abstract   bibtex   
Targeting guanine (G) quadruplex structures is an exciting new strategy with potential for controlling gene expression and designing anticancer agents. Guanine-rich peptide nucleic acid (PNA) oligomers bind to homologous DNA and RNA to form hetero-G-quadruplexes but can also bind to complementary cytosine-rich sequences to form heteroduplexes. In this study, we incorporated backbone modifications into G-rich PNAs to improve the selectivity for quadruplex versus duplex formation. Incorporation of abasic sites as well as chiral modifications to the backbone were found to be effective strategies for improving selectivity as shown by UV-melting and surface plasmon resonance measurements. The enhanced selectivity is due primarily to decreased affinity for complementary sequences, since binding to the homologous DNA to form PNA-DNA heteroquadruplexes retains high affinity. The improved selectivity of these PNAs is an important step toward using PNAs for regulating gene expression by G-quadruplex formation.
@article{Lusvarghi2009,
	title = {Loop and backbone modifications of peptide nucleic acid improve g-quadruplex binding selectivity},
	issn = {0002-7863 ST - Loop and Backbone Modifications of Peptide Nucleic Acid Improve G-Quadruplex Binding Selectivity},
	url = {http://dx.doi.org/10.1021/ja907250j},
	doi = {10.1021/ja907250j},
	abstract = {Targeting guanine (G) quadruplex structures is an exciting new strategy with potential for controlling gene expression and designing anticancer agents. Guanine-rich peptide nucleic acid (PNA) oligomers bind to homologous DNA and RNA to form hetero-G-quadruplexes but can also bind to complementary cytosine-rich sequences to form heteroduplexes. In this study, we incorporated backbone modifications into G-rich PNAs to improve the selectivity for quadruplex versus duplex formation. Incorporation of abasic sites as well as chiral modifications to the backbone were found to be effective strategies for improving selectivity as shown by UV-melting and surface plasmon resonance measurements. The enhanced selectivity is due primarily to decreased affinity for complementary sequences, since binding to the homologous DNA to form PNA-DNA heteroquadruplexes retains high affinity. The improved selectivity of these PNAs is an important step toward using PNAs for regulating gene expression by G-quadruplex formation.},
	journal = {Journal of the American Chemical Society},
	author = {Lusvarghi, Sabrina and Murphy, Connor T and Roy, Subhadeep and Tanious, Farial A and Sacui, Iulia and Wilson, W David and Ly, Danith H and Armitage, Bruce A},
	year = {2009},
	keywords = {\#nosource},
}

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