KINETIC-ANALYSIS OF SPECIFICITY OF DUPLEX DNA TARGETING BY HOMOPYRIMIDINE PEPTIDE NUCLEIC-ACIDS

A simple theoretical analysis shows that specificity of double-strande d DNA (dsDNA) targeting by homopyrimidine peptide nucleic acids (hpyPN As) is a kinetically controlled phenomenon. Our computations give the optimum conditions for sequence-specific targeting of dsDNA by hpyPNAs . The analysis shows that, in agreement with the available experimenta l data, kinetic factors play a crucial role in the selective targeting of dsDNA by hpyPNAs. The selectivity may be completely lost if PNA co ncentration is too high and/or during prolonged incubation of dsDNA wi th PNA. However, quantitative estimations show that the experimentally observed differences in the kinetic constants for hpyPNA binding with the correct and mismatched DNA sites are sufficient for sequence-spec ific targeting of long genomic DNA by hpyPNAs with a high yield under appropriate experimental conditions. Differential dissociation of hpyP NA/dsDNA complexes is shown to enhance the selectivity of DNA targetin g by PNA.