PNA hybridizes to complementary oligonucleotides obeying the Watson–Crick hydrogen-bonding rules

Abstract

DNA analogues are currently being intensely investigated owing to their potential as gene-targeted drugs. Furthermore, their properties and interaction with DNA and RNA could provide a better understanding of the structural features of natural DNA that determine its unique chemical, biological and genetic properties. We recently designed a DNA analogue, PNA, in which the backbone is structurally homomorphous with the deoxyribose backbone and consists of N-(2-aminoethyl)glycine units to which the nucleobases are attached. We showed that PNA oligomers containing solely thymine and cytosine can hybridize to complementary oligonucleotides, presumably by forming Watson-Crick-Hoogsteen (PNA)2-DNA triplexes, which are much more stable than the corresponding DNA-DNA duplexes, and bind to double-stranded DNA by strand displacement. We report here that PNA containing all four natural nucleobases hybridizes to complementary oligonucleotides obeying the Watson-Crick base-pairing rules, and thus is a true DNA mimic in terms of base-pair recognition.

Cellular delivery of a double-stranded oligonucleotide

“…PNA is a nucleic acid analogue consisting of an achiral polyamide backbone that has been shown to form stable and tight complexes with complementary DNA or RNA. 32,33 The PNA/DNA binding is 10-100 times stronger than DNA/DNA, a feature that can be used to form specific complexes of transport peptide-PNA and the oligonucleotide transcription factor decoy. After uptake, the disulfide bond is reduced in the cytoplasm, leading to the rapid dissociation of the PNA from the carrier peptide, 34 permitting PNA-NFkB decoy to associate with the NFkB/Rel transcription factor in the cytoplasm, or transport peptide-PNA-NFkB decoy may translocate to the nucleus and associate with the activated translocated NFkB transcription factor dimer ( Figure 1).…”

Light-Up Probes: Thiazole Orange-Conjugated Peptide Nucleic Acid for Detection of Target Nucleic Acid in Homogeneous Solution

“…We call them light-up probes. They are composed of thiazole orange (TO) 2 conjugated to peptide nucleic acid (PNA), and combine the excellent hybridization properties of PNA (8) with the extraordinary fluorescence enhancement of asymmetric cyanine dyes upon binding to nucleic acids (9). PNA binds sequence specifically to target nucleic acid bringing the dye to it.…”

“…Further, PNA-DNA duplexes can form both in parallel and in antiparallel orientation, and PNA 2 -DNA triplexes can form with the two PNA strands either parallel or antiparallel to the DNA. The PNA-DNA complexes vary considerably in thermal stability but are all much more stable than DNA duplexes (8).…”

Synthesis and Properties of Isobicyclo‐DNA

“…A large number of chemical modifications on the DNA bases, sugar and internucleoside linkage have been reported over the last two decades, but only a handful of those have been used in extensive pre-clinical or clinical tests. Amongst those are the class of 2'O-alkylated RNA, [4] the morpholino phosphorodiamidates, [5] the peptide nucleic acids (PNA) [6] and the locked nucleic acids (LNA) [7] .…”