γ-(S)-Guanidinylmethyl-Modified Triplex-Forming Peptide Nucleic Acids Increase Hoogsteen-Face Affinity for a MicroRNA and Enhance Cellular Uptake

Chembiochem. 2019 Dec 13;20(24):3041-3051. doi: 10.1002/cbic.201900393. Epub 2019 Sep 26.

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.

Keywords: 19F NMR spectroscopy; RNA triple helices; cellular uptake; peptide nucleic acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Guanidine / chemistry*
  • MicroRNAs / metabolism*
  • Nucleic Acid Conformation*
  • Peptide Nucleic Acids / chemistry*
  • Peptide Nucleic Acids / metabolism*

Substances

  • MicroRNAs
  • Peptide Nucleic Acids
  • Guanidine