Emissive nucleobases in PNA chemistry

Peptide nucleic acids (PNA) are key candidates in chemical biology. They are synthetic oligonucleotide mimetics which are capable of interacting with DNA and RNA due to common nucleobase alphabet, although presenting a pseudopeptide backbone. They have been already studied in antisense and antigene therapies, gene editing, nucleic acid sensing and imaging. The substitution of natural occurring nucleobases with fluorescent isomorphic analogues into PNA is a unique strategy to impart intrinsic luminescence while maintaining efficient paring, aiming to overcome structural limitations of fluorophores’ tagging.3 Isomorphic fluorescent bases have shown significant emissive read-outs upon variation of pH and polarity and in the imaging of biological relevant events like duplex formation. In this work we have prepared and investigated thieno[3,4-d]pyrimidine nucleobases and their incorporation into PNA. Our studies confirm how the synthesized bases are compatible for insertion along PNA sequences of different length to deeply understand the emissive traits and to evaluate the ability to form stable heteroduplex with complementary DNAs. These preliminary results highlight that these fluorescent analogues can be easily used for PNA synthesis while conferring significant modular luminescence.