Incorporating G‑C Pair-Recognizing Guanidiniuminto PNAs for Sequence and Structure Specific Recognition of dsRNAsover dsDNAs and ssRNAs

Recognition of RNAs at physiological conditions is important for developing chemical probes and therapeutic ligands. Nucleobase modified dsRNA-binding PNAs (dbPNAs) are promising for the recognition of dsRNAs in a sequence and structure specific manner at near-physiological conditions. Guanidinium is often present in proteins and small molecules for the recognition of G bases in nucleic acids, in cell-penetrating carriers, as well as in bioactive drug molecules, which might be due to the fact that guanidinium is amphiphilic with unique hydrogen bonding and stacking properties. We hypothesized that a simple guanidinium moiety can be directly incorporated into PNAs for facilitating enhanced molecular recognition of G-C pairs in dsRNAs and for improved bioactivity. We grafted guanidinium moiety directly into a PNA monomer (designated as R) using a two-carbon linker as guided by computational modeling studies. The synthetic scheme of PNA R monomer is relatively simple compared to that of previously reported L...