5‑Amidodansyl‑U (UD) Peptide Nucleic Acid (PNA) as a Fluorescent Sensor of the Local Dielectric Constant (ε) in PNA Duplexes: Major Grooves in PNA Duplexes Are More Hydrophobic Than Major Grooves in DNA–DNA Duplexes

Peptide nucleic acids (PNA) show great promise for the development of antisense drugs owing to their superior binding property with complementary DNA/RNA. They recognize complementary DNA/RNA/PNA via hydrogen bonding and electrostatic interaction whose strengths depend on their chemical environment. It is therefore important to understand the effects of local dielectrics in the major/minor grooves of PNA:DNA/RNA/PNA duplexes that influence its superior binding. By employing 5-amidodansyl U on PNA as a fluoroprobe of the local environment and measuring the polarity-sensitive Stokes shift, it is demonstrated that compared to the major groove of DNA–DNA duplexes, the analogous major groove of PNA:DNA/RNA/PNA duplexes is more hydrophobic (lower ε), and sequence-dependent polarity changes are seen in all PNA duplexes. The results highlight the effects of chemical modifications of backbone and base sequence in nucleic acids on the local environment of grooves, leading to a dielectric continuum that may have implications for the binding of ligands and macromolecules in grooves of nucleic acid duplexes.