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Updated: Aug 4, 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
Single-strand-targeted triplex formation: stability, specificity and RNase H activation properties
1Hybridon, Inc., Worcester, MA 01605.
Abstract:
Single-stranded (ss) oligodeoxyribonucleotides (oligos) containing both Watson-Crick and Hoogsteen hydrogen bonding domains joined by either a 5-nucleotide loop or a flexible hexaethylene-glycol linker, called foldback triplex-forming oligos (FTFOs), are designed and studied for their binding affinity and specificity to their ss DNA/RNA targets. Thermal denaturation studies revealed an increased affinity of FTFOs, due to addition of a Hoogsteen hydrogen bonding domain at the binding site, as the Watson-Crick domain forms a double helix with the target, when compared to conventional antisense and antigene oligos. DNase I hydrolysis and electrophoretic mobility shift analysis confirmed the formation of foldback triplexes relative to conventional double- and triple-stranded structures. The FTFOs showed increased sequence specificity mainly arising from their ability to recognize the target sequence twice, first by Watson-Crick base pairing and a second time by Hoogsteen base pairing. An FTFO with DNA components in both duplex- and triplex-forming domains showed preference for a DNA homopurine target strand.
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