Synthesis and physicochemical properties of 20-mer peptide nucleic acid conjugates with testosterone 17β-carboxylic acid

Abstract

Although peptide nucleic acids (PNAs) have improved nuclease resistance compared with DNA or RNA, it is difficult to synthesize long PNAs because of poor elongation yield. Herein we synthesized 20-mer PNAs (PNA20), targeting Nnmt mRNA, as well as its conjugate with testosterone 17β-carboxylic acid, in high purity and yield. This synthesis was conducted using Oxyma as a condensation agent and NMP as a solvent for Fmoc-PNA-C(Bhoc)-OH. The resistance of PNA20 to exonuclease was higher than that of RNA. Furthermore, the abilities of PNA20 and its conjugate to bind to complementary DNA were stronger than that of DNA or RNA. These findings lay the basis for the synthesis of long PNA derivatives toward oligonucleotide therapeutics.