PNA conjugated to high-molecular weight poly(ethylene glycol): Synthesis and properties

Peptide nucleic acids (PNAs) are able to recognize and bind to a specific DNA or RNA strand with high affinity and selectivity, superior to analogous oligonucleotide sequences. These derivatives have high chemical stability, and their resistance to nucleases and proteases make them good candidates as therapeutic agents, diagnostic tools, and probes in molecular biology.([1]) However, a practical limitation is their low water solubility and high tendency toward self-aggregation. Moreover, a facile and useful system of delivery is still demanded and several methods have been proposed to improve their cellular uptake, as peptides,([2]) cationic liposomes,([3]) and lipophilic ligands.([4]) In this regard, the conjugation of PNAs with the amphiphilic, atoxic, and largely soluble poly(ethylene glycol)s (PEGs) can be evaluated to increase their solubility in aqueous media, as well as to improve their cell membrane permeability and resistance to enzymatic degradation, using the same approach previously described for oligonucleotides.([5])