Heterocyclic aromatic peptide nucleic acids

In order to investigate the role played by the aromatic moiety of Aromatic Peptide Nucleic Acids (APNAs) in their ability to hybridize with RNA and DNA, as well as improve the solubility of APNA oligomers in aqueous solutions, a new generation of heterocyclic monomers were designed. APNA monomers, where the nucleobase can be thymine, cytosine adenine or guanine, with backbones contain thiophene and pyridine moieties were synthesized. Suitably protected APNA-APNA and PNA-APNA dimers were also synthesized as building blocks for the solid phase synthesis of APNA-PNA chimeras and APNA homopolymers. Due to the instability of the pyridine-containing APNA oligomers to the harsh acidic conditions required to cleave oligomers from the MBHA resin, a new protocol was developed for the synthesis of these molecules on the trityl chloride resin. Oligomers of PNA and APNA-PNA chimeras were successfully synthesized on this solid support, and cleaved from the resin using mild acidic conditions.