Variation of Tetrahydrofurans in Thyclotides Enhances Oligonucleotide Binding and Cellular Uptake of Peptide Nucleic Acids

Selective incorporation of conformational constraints into thyclotides can be used to modulate their binding complementary oligonucleotides, increase polarity, and optimize uptake HCT116 cells without assistance from moieties known promote cell uptake. The X-ray structure biophysical studies a thyclotide–DNA duplex reveal that tetrahydrofurans an aegPNA backbone promotes helical conformation enhances DNA RNA. the allows polarity increased incrementally so optimized. enhanced binding, cellular properties were demonstrate effective inhibition microRNA-21 in cells.