Synthesis of peptide - Peptide Nucleic Acid conjugates
Peptide nucleic acids (PNAs), developed by Peter Nielsen in the early 90’s, constitute synthetic analogues of DNA and RNA, where the phosphodiester backbone of these natural oligonucleotides (ON) is replaced by a pseudopeptide structure. PNAs hybridize with complementary nucleic acid segments with higher affinity and specificity than natural ON, interfering with higher efficiency with target genes. Moreover, the unnatural backbone of PNAs makes them highly resistant to enzymatic degradation.
These characteristics make them valuable tools for various applications, from diagnostics to therapeutics. Limitations to their versatility include poor water solubility and low nuclear targeting capability. However, these have been successfully circumvented by the introduction of chemical modifications to PNA sequences, such as cell-penetrating peptides, which have been proven to be highly valuable in drug delivery and gene therapy. Just as for peptides, PNA can be obtained through standard SPPS procedures.
View the recording to hear a brief introduction of these ON analogues and address the synthesis of a target peptide-PNA sequence, particularly highlighting the differences between manual and automated approaches, using Symphony® X peptide synthesizer from Gyros Protein Technologies, and the challenges we faced during this process.