Figure 1.

a) Structures of three natural methylated cytidines and their structural consequences. m³C blocks the Watson–Crick (WC) edge and confers a positive charge to the nucleobase. m⁴C retains WC base pairing in anti‐conformation which is destabilized by steric clash between 5‐H and N ⁴‐Me. In syn‐conformation, m⁴C hinders WC base pairing. m⁵C enhances hydrophobicity in the major groove and improves base stacking. b) Design of in vitro selection libraries. Splint for ligation and primer binding sites are indicated. Detailed selection is shown in Figure S1.