Figure 1.

Thyclotide, a miR-21 targeting PNA-based molecule bearing tetrahydrofuran rings in the backbone. (A) Secondary structure of pre-miR-21 (top) and sequence of mature hsa-miR-21-5p (bottom). The seed sequence of mature miR-21 is in red. (B) Structural schematic of the regular aegPNA (left) and thyclotide (right) and the 14-nucleobase sequences representing aegPNA 1 and thyclotide 2. Thyclotides possess tetrahydrofuran rings in the backbone, designated by red in the chemical drawing and by the symbol * in the sequence. (C) Normalized UV melting curves of aegPNA 1 and thyclotide 2 with their complementary DNA. The T_m of the aegPNA-DNA duplex is 64°C. The T_m of the thyclotide-DNA duplex is likely >95°C and could not be accurately calculated.