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Updated: May 14, 2026

Sequence-specific and Selective Recognition of Double-stranded RNAs over Single-stranded RNAs by Chemically Modified Peptide Nucleic Acids
Published on: September 21, 2017
The size of the aryl linker between two polyaza-cyclophane moieties controls the binding selectivity to ds-RNA vs.
Jorge González-García1, Lidija Uzelac, Marijeta Kralj
1ICMOL, Departamento de Química Inorgánica, Facultad de Química, Universidad de Valencia, C/Catedrático José Beltrán 2, 46980 Paterna, Valencia, Spain.
Abstract:
Aryl-linked (pyridine- vs. phenanthroline-) bis-polyaza pyridinophane scorpiands PYPOD and PHENPOD strongly bind to the double stranded DNA and RNA, whereby very intriguing RNA over DNA selectivity is finely tuned by aryl-linker length and aromatic surface. Moreover, PYPOD and PHENPOD dimer formation at high compound/polynucleotide ratios is highly sensitive to the fine interplay between the steric and binding properties of compound-dimers and the DNA minor groove/RNA major groove. That is demonstrated by significantly different induced CD spectra, which allow spectroscopic differentiation between various DNA/RNA secondary structures. A significantly higher (micromolar) antiproliferative effect of PYPOD and PHENPOD on human cell lines with respect to previously reported pyridine-based tripodal aliphatic polyamines is attributed to masked positive charges and increased hydrophobicity of novel compounds, resulting in more efficient membrane permeation and cellular uptake.
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