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

M Eriksson, G Haaima, L Orgel, Peter E. Nielsen

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 degrees 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.

OriginalsprogEngelsk
TidsskriftNew Journal of Chemistry
Vol/bind22
Sider (fra-til)1055-9
Antal sider5
ISSN0398-9836
StatusUdgivet - 1998

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