Building on the peptide nucleic acid (PNA) scaffold: a biomolecular engineering approach

Peptide nucleic acids (PNAs) are polyamide analogues of nucleic acids, very effective in terms of affinity and selectivity in DNA/RNA recognition. As other supramolecular entities, the PNA structure has been an interesting scaffold for the development of new molecules, aimed to DNA and RNA recognition, with improved or completely new properties. This review describes recent work, with the aim of describing how the design of these molecules has evolved in recent years, using increasingly effective tools, from simple crystal structure analysis to molecular dynamics and metadynamics. Modified PNA with additional modules appended, either on the backbone or on the nucleobase, are described. Polyfunctional molecules with both backbone and nucleobase modification are then considered. Finally, recent examples of architectures obtained by conjugation of PNAs to inorganic nanostructures as cargo systems for diagnostics and nano-biotechnology are presented.