Synthesis of aromatic peptide nucleic acids

The synthesis of two analogues of Aromatic Peptide Nucleic Acids (APNAs) monomers was successfully achieved. These Peptide Nucleic Acid analogues could be used as building blocks for the synthesis of oligomers with the DNA and RNA recognition properties of PNAs in addition to a more hydrophobic backbone which may improve cell permeability. Such analogues may be useful as antisense/antigene therapeutic agents.;A first generation APNA hexamer, composed of monomers of general structure A was synthesized in solution. Thermal denaturation studies failed to indicate if these compounds hybridize to DNA or RNA. The second generation APNA monomers (B) were incorporated into PNA hexamers by solid phase peptide synthesis. The resulting PNA/APNA chimeras hybridize to both DNA and RNA by triple helix formation, however these complexes were found to be less stable than the unmodified PNAs.