Thiazole Containing PNA Mimic Regulates Gene Expression through DNA G-Quadruplex.

Peptide nucleic acids (PNAs), besides hybridizing to complementary DNA and RNAs, bind and stabilize DNA secondary structures. Herein, we illustrate the design and synthesis of PNA-like scaffolds by incorporating five-membered thiazole rings as modified bases instead of nucleobases and their subsequent effects on gene regulation by biophysical and assays. A thiazole-modified PNA trimer selectively recognizes G-quadruplex (G4) DNA over other G4s and duplex DNA. It displays a high stabilization potential for the G4 DNA and shows remarkable fluorescence enhancement with the G4. It is flexible enough to bind at 5' and 3' ends as well as in the groove region of G4. Furthermore, the PNA trimer easily permeates the cellular membrane and suppresses mRNA expression in HeLa cells by targeting the promoter G4. This study illuminates modified PNAs as flexible molecular tools for selective targeting of noncanonical nucleic acids and modulating gene function.