Abstract
Regulation of genetic functions based on targeting DNA or RNA sequences with complementary oligonucleotides is especially attractive in the post-genome era. Oligonucleotides can be rationally designed to bind their targets based on simple nucleic acid base pairing rules. However, the use of natural DNA and RNA oligonucleotides as targeting probes can cause numerous off-target effects. In addition, natural nucleic acids are prone to degradation in vivo by various nucleases. To address these problems, nucleic acid mimics such as peptide nucleic acids (PNA) have been developed. They are more stable, show less off-target effects, and, in general, have better binding affinity to their targets. However, their high affinity to DNA can reduce their sequence-specificity. The formation of alternative DNA secondary structures, such as the G-quadruplex, provides an extra level of specificity as targets for PNA oligomers. PNA probes can target the loops of G-quadruplex, invade the core by forming PNA-DNA guanine-tetrads, or bind to the open bases on the complementary cytosine-rich strand. Not only could the development of such G-quadruplex-specific probes allow regulation of gene expression, but it will also provide a means to clarify the biological roles G-quadruplex structures may possess.
Keywords: Peptide Nucleic Acids, G-quadruplex, gene expression regulation, guanines, Oligonucleotides, cytosine-rich strand, charge-charge interactions, rigidification, antigene, purine bases
Current Pharmaceutical Design
Title:Targeting DNA G-Quadruplex Structures with Peptide Nucleic Acids
Volume: 18 Issue: 14
Author(s): Igor G. Panyutin, Mykola I. Onyshchenko, Ethan A. Englund, Daniel H. Appella and Ronald D. Neumann
Affiliation:
Keywords: Peptide Nucleic Acids, G-quadruplex, gene expression regulation, guanines, Oligonucleotides, cytosine-rich strand, charge-charge interactions, rigidification, antigene, purine bases
Abstract: Regulation of genetic functions based on targeting DNA or RNA sequences with complementary oligonucleotides is especially attractive in the post-genome era. Oligonucleotides can be rationally designed to bind their targets based on simple nucleic acid base pairing rules. However, the use of natural DNA and RNA oligonucleotides as targeting probes can cause numerous off-target effects. In addition, natural nucleic acids are prone to degradation in vivo by various nucleases. To address these problems, nucleic acid mimics such as peptide nucleic acids (PNA) have been developed. They are more stable, show less off-target effects, and, in general, have better binding affinity to their targets. However, their high affinity to DNA can reduce their sequence-specificity. The formation of alternative DNA secondary structures, such as the G-quadruplex, provides an extra level of specificity as targets for PNA oligomers. PNA probes can target the loops of G-quadruplex, invade the core by forming PNA-DNA guanine-tetrads, or bind to the open bases on the complementary cytosine-rich strand. Not only could the development of such G-quadruplex-specific probes allow regulation of gene expression, but it will also provide a means to clarify the biological roles G-quadruplex structures may possess.
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Cite this article as:
G. Panyutin Igor, I. Onyshchenko Mykola, A. Englund Ethan, H. Appella Daniel and D. Neumann Ronald, Targeting DNA G-Quadruplex Structures with Peptide Nucleic Acids, Current Pharmaceutical Design 2012; 18 (14) . https://dx.doi.org/10.2174/138161212799958440
DOI https://dx.doi.org/10.2174/138161212799958440 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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