Optimizing automated synthesis of peptide nucleic acids
By Biotage
Peptide nucleic acids (PNAs) continue to gain traction in diagnostic and potentially therapeutic applications where oligonucleotides are the current modality of interest. Despite containing an unnatural backbone, PNA-based mimetics retain the well-established, high fidelity hybridization properties associated with naturally occurring
oligonucleotides. As oligonucleotides are approved as therapeutics, PNAs also increase in attractiveness given their resistance to nucleases and proteases, a chemically neutral backbone and synthetic tractability.
Despite these perceived advantages, PNAs have received little traction given their synthetic difficulty and cost. Although synthetically similar strategies are employed when compared to solid phase peptide synthesis, alternative strategies are often employed to overcome significant steric effects that compromise synthetic success. Herein we discuss several strategies toward optimizing automated synthesis of difficult PNA compounds including resin type and substitution level, reaction time and others all while minimizing monomer consumption.
Literature number: P244
