Tetrahydrofuran Peptide Nucleic Acids.

Peptide nucleic acids (PNAs) have attracted considerable attention in biomedical research due to their strong binding properties toward complementary oligonucleotides and complete resistance to enzymatic degradation. However, the applications of PNAs may be limited by poor cellular uptake and low water solubility. To this end, we introduced rigid tetrahydrofurans (thfs) into the PNA backbone to develop tetrahydrofuran peptide nucleic acids (thfPNAs) with significant improvements in binding properties, water solubility, and cellular uptake. Herein we describe the protocols for preparing thfPNA monomers, thfPNA oligomers, and methods to study their cellular uptake using FACS experiments.