Sequence dependent N-terminal rearrangement and degradation of peptide nucleic acid (PNA) in aqueous solution.
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.
Eriksson
M
M
Dept. of Biochemistry B, The Panum Institute, Copenhagen, Denmark.
Christensen
L
L
Schmidt
J
J
Haaima
G
G
Orgel
L
L
Nielsen
P E
PE
D019418:Evolution, Chemical; D006863:Hydrogen-Ion Concentration; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D012996:Solutions; D013941:Thymine / Q000031:analogs & derivatives*; D014867:Water / Q000737:chemistry*
D020135:Peptide Nucleic Acids; D011108:Polymers; D012996:Solutions; D014867:Water; D013941:Thymine