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

: Tähtinen V, Verhassel A, Tuomela J, Virta P

Publisher: WILEY-V C H VERLAG GMBH

: WEINHEIM

: 2019

: ChemBioChem

: CHEMBIOCHEM

: 20

: 24

: 3041

: 3051

: 12

: 1439-4227

DOI: https://doi.org/10.1002/cbic.201900393(external)

: https://research.utu.fi/converis/portal/detail/Publication/42614349(external)

gamma-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 gamma-(S)-guanidinylmethyl modifications increased the affinity and Hoogsteen-face selectivity for the miR-215 model without ternary (PNA)(2)/RNA complex formation. Moreover, the gamma-(S)-guanidinylmethyl groups were observed to facilitate internalization of the TFPNAs into living PC-3 prostate cancer cells.

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