Triplex-forming oligonucleotides inhibit gene expression by:
Triplex-forming oligonucleotides polypurine tracts 15-30 nucleotides bind major groove duplex DNA without unwinding helix forming Hoogsteen or reverse Hoogsteen hydrogen bonds with purine strand Watson-Crick duplex generating three-stranded structure requiring homopurine-homopyrimidine mirror repeats where one strand purine-rich. Formation stabilized N3 protonated cytosine acidic pH binding G-C base pair or using 5-methylcytosine or pseudoisocytosine allowing neutral pH triple helix. When targeted promoter enhancer oncogene c-myc P2 promoter 27 bp purine tract, triple helix sterically occludes
Ref: PubMed Triplex Inhibition 28412345; Nature Struct Biol Triple Helix; Watson Molecular Biology DNA Triplex Chap 5.
