BIOMAT Database Logo BIOMAT Database Logo

Kinetic analysis of specificity of duplex DNA targeting by homopyrimidine peptide nucleic acids. 1997

V V Demidov, and M V Yavnilovich, and M D Frank-Kamenetskii
Center for Advanced Biotechnology, Department of Biomedical Engineering, Boston University, Massachusetts 02215, USA. vvd@enga.bu.edu

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.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008956 Models, Chemical Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment. Chemical Models,Chemical Model,Model, Chemical
D009696 Nucleic Acids High molecular weight polymers containing a mixture of purine and pyrimidine nucleotides chained together by ribose or deoxyribose linkages. Nucleic Acid,Acid, Nucleic,Acids, Nucleic
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D011743 Pyrimidines A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D001703 Biophysics The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things. Mechanobiology
D055592 Biophysical Phenomena The physical characteristics and processes of biological systems. Biophysical Concepts,Biophysical Processes,Biophysical Phenomenon,Biophysical Process,Biophysical Concept,Concept, Biophysical,Concepts, Biophysical,Phenomena, Biophysical,Phenomenon, Biophysical,Process, Biophysical,Processes, Biophysical

Related Publications

V V Demidov, and M V Yavnilovich, and M D Frank-Kamenetskii
Sequence-selective targeting of duplex DNA by peptide nucleic acids.
April 2010, Current opinion in molecular therapeutics,
V V Demidov, and M V Yavnilovich, and M D Frank-Kamenetskii
Sequence-specific targeting of duplex DNA by peptide nucleic acids via triplex strand invasion.
February 2001, Methods (San Diego, Calif.),
V V Demidov, and M V Yavnilovich, and M D Frank-Kamenetskii
Silencing gene expression by targeting chromosomal DNA with antigene peptide nucleic acids and duplex RNAs.
January 2006, Nature protocols,
V V Demidov, and M V Yavnilovich, and M D Frank-Kamenetskii
Superior duplex DNA strand invasion by acridine conjugated peptide nucleic acids.
May 2003, Journal of the American Chemical Society,
V V Demidov, and M V Yavnilovich, and M D Frank-Kamenetskii
Magnetic peptide nucleic acids for DNA targeting.
October 2009, Chemical communications (Cambridge, England),
V V Demidov, and M V Yavnilovich, and M D Frank-Kamenetskii
Targeting DNA G-quadruplex structures with peptide nucleic acids.
January 2012, Current pharmaceutical design,
V V Demidov, and M V Yavnilovich, and M D Frank-Kamenetskii
Strand displacement and duplex invasion into double-stranded DNA by pyrrolidinyl peptide nucleic acids.
September 2015, Organic & biomolecular chemistry,
V V Demidov, and M V Yavnilovich, and M D Frank-Kamenetskii
Targeting peptide nucleic acid-protein conjugates to structural features within duplex DNA.
April 1995, Bioorganic & medicinal chemistry,
V V Demidov, and M V Yavnilovich, and M D Frank-Kamenetskii
Recognition of chromosomal DNA in human cells by peptide nucleic acids and small duplex RNAs.
November 2005, Annals of the New York Academy of Sciences,
V V Demidov, and M V Yavnilovich, and M D Frank-Kamenetskii
Site-specific discrimination of Cytosine and 5-methylcytosine in duplex DNA by Peptide nucleic acids.
September 2002, Journal of the American Chemical Society,
Copied contents to your clipboard!