Triplex-Forming Peptide Nucleic Acids as Emerging
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levi123Triplex-Forming Peptide Nucleic Acids as Emerging
Uploaded by
levi123Triplex-forming peptide nucleic acids as emerging ligands
to modulate structure and function of complex RNAs
Katkevics, M., MacKay, J., Rozners, E.
Chemical Communications (DOI: 10.1039/d3cc05409h)
Generated on April 13, 2025
Triplex-forming peptide nucleic acids as emerging ligands
to modulate structure and function of complex RNAs
Abstract
<jats:p>Over the last three decades, triplex-forming PNAs have emerged as ligands for the recognition
of double-stranded RNA. Strong and sequence selective binding using synthetic nucleobases offers
opportunity for modulation of biological function of endogenous RNA transcripts.</jats:p>
* Corresponding authors
a Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga, LV-1006, Latvia
b Department of Chemistry and Biochemistry, Elizabethtown College, Elizabethtown, PA 17022, USA
c Department of Chemistry, Binghamton University, Binghamton, NY 13902, USA E-mail:
[email protected]
Over the last three decades, our view of RNA has changed from a simple intermediate supporting
protein synthesis to a major regulator of biological processes. In the expanding area of RNA research,
peptide nucleic acid (PNA) is emerging as a promising ligand for triple-helical recognition of complex
RNAs. As discussed in this feature article, the key advantages of PNAs are high sequence specificity
and affinity for RNA (>10 fold higher than for DNA) that are difficult to achieve with small molecule
ligands. Emerging studies demonstrate that triple-helical binding of PNAs can modulate biological
function and control dynamic conformational equilibria of complex folded RNAs. These results suggest
that PNA has a unique potential as a research tool and therapeutic compound targeting RNA. The
remaining problems hampering advances in these directions are limitations of sequences that can be
recognized by Hoogsteen triplexes (typically purine rich tracts), poor cellular uptake and bioavailability
of PNA, and potential off-target effects in biological systems. Recent exciting studies are discussed that
illustrate how synthetic nucleic acid chemistry provides innovative solutions for these problems.
