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:NIH/CC/RAD&IS, Bldg. 10, Rm. 1C401, Bethesda, MD 20892-1180 USA.
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.
