Kinetic analysis of specificity of duplex DNA targeting by homopyrimidine peptide nucleic acids

Biophysical Journal
Vadim V DemidovM D Frank-Kamenetskii

Abstract

A simple theoretical analysis shows that specificity of double-stranded DNA (dsDNA) targeting by homopyrimidine peptide nucleic acids (hpyPNAs) 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 experimental data, kinetic factors play a crucial role in the selective targeting of dsDNA by hpyPNAs. The selectivity may be completely lost if PNA concentration is too high and/or during prolonged incubation of dsDNA with 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-specific targeting of long genomic DNA by hpyPNAs with a high yield under appropriate experimental conditions. Differential dissociation of hpyPNA/dsDNA complexes is shown to enhance the selectivity of DNA targeting by PNA.

Citations

Dec 14, 2004·Chembiochem : a European Journal of Chemical Biology·Peter E NielsenCarsten Behrens
Apr 23, 2004·Trends in Biochemical Sciences·Vadim V Demidov, Maxim D Frank-Kamenetskii
Jan 1, 2000·Journal of Biomolecular Structure & Dynamics·H KuhnM D Frank-Kamenetskii
Dec 25, 2003·Journal of Biomolecular Structure & Dynamics·Olga V KrupnikYurii S Lazurkin
Aug 9, 2001·Antioxidants & Redox Signaling·R Owen, T R Flotte
Jul 11, 2003·Nucleic Acids Research·Ekaterina ProtozanovaMaxim D Frank-Kamenetskii
Dec 4, 2015·International Journal of Molecular Sciences·Bénédicte NdebokoLucyna Cova
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Feb 25, 2021·Journal of Computer-aided Molecular Design·Christopher M Topham, Jeremy C Smith
Feb 22, 2001·Methods : a Companion to Methods in Enzymology·V V Demidov, M D Frank-Kamenetskii

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