LAUSR

γ‐Modified (i.e., (S)‐aminomethyl, (S)‐acetamidomethyl, (R)‐4‐(hydroxymethyl)triazol‐1‐ylmethyl, and (S)‐guanidinylmethyl) triplex‐forming peptide nucleic acids (TFPNAs) were synthesized and the effect of the backbone modifications on the binding to a miR‐215 model was studied. Among the modifications, an appropriate pattern of three γ‐(S)‐guanidinylmethyl modifications increased the affinity and Hoogsteen‐face selectivity for the miR‐215 model without ternary (PNA)2/RNA complex formation. Moreover, the γ‐(S)‐guanidinylmethyl groups were observed to facilitate internalization of the TFPNAs into living PC‐3 prostate cancer cells.