Sequence dependent N-terminal rearrangement and degradation of peptide nucleic acid (PNA) in aqueous solution

Abstract

The stability of the PNA (peptide nucleic acid) thymine monomer {N-[2-(thymin-1-ylacetyl)]-N-(2-aminoaminoethyl)glycine} and those of various PNA oligomers (5–8-mers) have been measured at room temperature (20°C) as a function of pH. The thymine monomer undergoes N-acyl transfer rearrangement with a half-life of 34 days at pH 11 as analyzed by ¹H NMR; and two reactions, the N-acyl transfer and a sequential degradation, are found by HPLC analysis to occur at measurable rates for the oligomers at pH 9 or above. Dependent on the amino-terminal sequence, half-lives of 350 h to 163 days were found at pH 9. At pH 12 the half-lives ranged from 1.5 h to 21 days. The results are discussed in terms of PNA as a gene therapeutic drug as well as a possible prebiotic genetic material.