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γ‐( S )‐Guanidinylmethyl‐Modified Triplex‐Forming Peptide Nucleic Acids Increase Hoogsteen‐Face Affinity for a MicroRNA and Enhance Cellular Uptake
Author(s) -
Tähtinen Ville,
Verhassel Alejandra,
Tuomela Johanna,
Virta Pasi
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900393
Subject(s) - nucleic acid , peptide nucleic acid , chemistry , peptide , internalization , combinatorial chemistry , microrna , selectivity , rna , biochemistry , stereochemistry , cell , gene , catalysis
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.