Department of Chemistry, University of Turku, Vatselankatu 2, 20014, Turku, Finland.
FICAN West Cancer Research Laboratory, University of Turku and Turku University Hospital, Institution of Biomedicine, Medisiina D, Kiinamyllynkatu 10, 20520, Turku, Finland.
Chembiochem. 2019 Dec 13;20(24):3041-3051. doi: 10.1002/cbic.201900393. Epub 2019 Sep 26.
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) /RNA complex formation. Moreover, the γ-(S)-guanidinylmethyl groups were observed to facilitate internalization of the TFPNAs into living PC-3 prostate cancer cells.
γ-修饰（即（S）-氨甲基、（S）-乙酰氨甲基、（R）-4-（羟甲基）三唑-1-基甲基和（S）-胍基甲基）三聚体形成肽核酸（TFPNAs）被合成，并研究了骨架修饰对与 miR-215 模型结合的影响。在这些修饰中，适当数量的三个 γ-（S）-胍基甲基修饰增加了与 miR-215 模型的亲和力和 Hoogsteen 面选择性，而没有三元（PNA）/RNA 复合物的形成。此外，观察到 γ-（S）-胍基甲基基团有助于 TFPNAs 进入活的 PC-3 前列腺癌细胞内。
