Loop and backbone modifications of peptide nucleic acid improve g-quadruplex binding selectivity.
Loop and backbone modifications of peptide nucleic acid improve g-quadruplex binding selectivity.
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DOI:
10.1021/ja907250j
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发表时间:
2009-12-30
影响因子:
15
通讯作者:
Armitage, Bruce A.
中科院分区:
文献类型:
--
作者:
Lusvarghi, Sabrina;Murphy, Connor T.;Roy, Subhadeep;Tanious, Farial A.;Sacui, Iulia;Wilson, W. David;Ly, Danith H.;Armitage, Bruce A.
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 vs 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.
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