PNA: Bridging the Protein and Nucleic Acid Worlds

We often think of proteins and nucleic acids in terms of a progression, i.e. DNA leads to RNA which leads to protein, or cooperation, e.g. RNA-protein assemblies like the ribosome or polymerase enzymes that replicate or transcribe DNA. In other words, these two classes of biomolecules often work together or depend on one another, but their chemical structures are distinct. Synthetic chemistry gives us the ability to covalently link peptide and nucleic acid units together to make conjugates which exhibit and leverage the properties of both. A fundamentally different structure, peptide nucleic acid (PNA) was reported in 1991 and fully integrates the two classes, with hydrogen-bonding nucleobases (G, A, C and T) covalently attached as side chains to a polyamide backbone. Over the ensuing three decades, numerous applications of PNA in biomedical research and clinical diagnostics have been reported and a wide variety of second generation PNAs have been reported. This seminar will provide an introduction to PNA and then focus on recent developments with a backbone-substituted analogue known as gammaPNA, which exhibits significantly improved affinity and better biocompatibility compared to the original PNA. In particular, the unique combination of protein- and nucleic acid-like properties of PNA has enabled important advances in the areas of cell delivery and DNA/RNA imaging and detection.