γ‐(<i>S</i>)‐Guanidinylmethyl‐Modified Triplex‐Forming Peptide Nucleic Acids Increase Hoogsteen‐Face Affinity for a MicroRNA and Enhance Cellular Uptake

Abstract

Abstract 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.