PNA hybridizes to complementary oligonucleotides obeying the Watson–Crick hydrogen-bonding rules

  title={PNA hybridizes to complementary oligonucleotides obeying the Watson–Crick hydrogen-bonding rules},
  author={M. Egholm and O. Buchardt and L. Christensen and C. Behrens and S. Freier and D. Driver and R. H. Berg and Seog K. Kim and B. Nord{\'e}n and P. Nielsen},
DNA ANALOGUES are currently being intensely investigated owing to their potential as gene-targeted drugs1–3. Furthermore, their properties and interaction with DNA and RNA could provide a better understanding of the structural features of natural DNA that determine its unique chemical, biological and genetic properties3,4. We recently designed a DNA analogue, PNA, in which the backbone is structurally homomorphous with the deoxyribose backbone and consists of N-(2-aminoethyl)glycine units to… Expand
Chemical Synthesis of Conformationally Constrained PNA Monomers
Peptide nucleic acid (PNA) 1 (Figure 1) is an oligopeptide with nucleobases linked together by an achiral, uncharged aminoethylglycine backbone (aeg-PNA), that binds strongly and in aExpand
The many faces of PNA
Peptide nucleic acids or PNA (Figure 1) were originally conceived as mimics of triple helix forming oligonucleotides designed for sequence specific targeting of double stranded DNA via major grooveExpand
A pyrenyl-PNA probe for DNA and RNA recognition
A systematic study on the binding properties of this probe towards DNA and RNA complementary strands was carried out by UV and fluorescence spectroscopy, indicating that the PNA probe bind more tightly to RNA rather than to DNA. Expand
Unique properties of purine/pyrimidine asymmetric PNA.DNA duplexes: differential stabilization of PNA.DNA duplexes by purines in the PNA strand.
The results so far do not allow us to identify the origin of the different stabilities of homopurine/homopyrimidine PNA, but the evidence does point to a significant structural component, which involves enthalpic contributions both within the duplex structure and also from bound water molecules. Expand
DNA Binding of A D‐Lysine‐Based Chiral PNA: Direction Control and Mismatch Recognition
Peptide nucleic acids (PNAs) are oligonucleotide analogues with a skeleton made up of N-(2-aminoethyl)glycine units; they bind to complementary DNA and RNA with high stability and specificity. InExpand
Peptide nucleic acids: a new dimension to peptide libraries and aptamers.
  • P. Nielsen
  • Biology, Medicine
  • Methods in enzymology
  • 1996
PNA functions as an artificial transcription factor and presents the potential of developing specific gene activation drugs and the stable and sequence-specific complexes, between PNA and RNA, make PNA an interesting DNA analog in an antisense drug context. Expand
Antisense properties of peptide nucleic acids.
Some recent achievements on PNA antisense application are summarized, especially these concerned with whole cell or tissue delivery of the PNA, which suggests that they could potentially serve as efficient antisense or antigene reagents. Expand
Peptide nucleic acid Hoogsteen strand linker design for major groove recognition of DNA thymine bases
Computational methods and spatial constraints derived from the experimental structure of a homopyrimidine PNA·DNA-PNA hetero-triplex are used to investigate the influence of linker flexibility on binding interactions of the E-base with thymine and uracil bases in geometry-optimised model systems. Expand
Structural characteristics of cyclopentane-modified peptide nucleic acids from molecular dynamics simulations
A PNA molecule is a DNA strand where the sugar-phosphate backbone has been replaced by a structurally homomorphous pseudopeptide chain consisting of N (2-amino-ethyl)-glycine units. PNA bindsExpand
Conformational and energetic properties of pyrrolidinyl PNA-DNA duplexes: A molecular dynamics simulation
Abstract The binding capability of pyrrolidinyl peptide nucleic acids (PNAs) to DNA have been studied experimentally, also the high affinity and sequence specificity were reported. However, to date aExpand


DNA unwinding upon strand-displacement binding of a thymine-substituted polyamide to double-stranded DNA.
This model may provide a general way in which to obtain sequence-specific recognition of any sequence in double-stranded DNA by Watson-Crick hydrogen-bonding base-pair recognition, and it is thus paramount to rigorously establish this binding mode for synthetic DNA-binding ligands. Expand
Sequence-selective recognition of DNA by strand displacement with a thymine-substituted polyamide.
The results show that the backbone of DNA can be replaced by a polyamide, with the resulting oligomer retaining base-specific hybridization. Expand
Peptide nucleic acids containing adenine or guanine recognize thymine and cytosine in complementary DNA sequences
Peptide nucleic acid (PNA) monomer building blocks for the introduction of G and A are prepared and used to synthesise H-T4XT5-Lys-NH2(X = G or A), which are shown by Tm measurements to recognizeExpand
Antisense and antigene properties of peptide nucleic acids.
Nuclear microinjection of cells constitutively expressing SV40 large T antigen with either a 15-mer or 20-mer PNA targeted to the T Ag messenger RNA suppressed T Ag expression, and Binding of PNAs to RNA resulted in site-specific termination of both reverse transcription and in vitro translation. Expand
Peptide nucleic acids (PNAs): potential antisense and anti-gene agents.
It is shown that primer extension by Taq DNA polymerase on a single-stranded template is arrested at an occupied PNA T10 binding site, and these results are discussed in relation to PNAs as potential anti-sense and anti-gene drugs. Expand
The contribution of DNA single-stranded order to the thermodynamics of duplex formation.
  • G. Vesnaver, K. Breslauer
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1991
The results demonstrate that despite being only marginally stable at 25 degree C, single strands can exhibit intramolecular interactions that poise them for duplex formation, and this behavior results from enthalpy and entropy contributions of similar magnitudes that compensate each other, thereby giving rise to relatively small free energies of stabilization for the single strands at 25 degrees C. Expand
Stability of ribonucleic acid double-stranded helices.
Abstract The hypochromicity, as a function of temperature for 19 oligoribonucleotides capable of forming perfectly base-paired double helices, is used to extract thermodynamic parameters of helixExpand
A model for the RNA-catalyzed replication of RNA.
  • T. Cech
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1986
It seems possible that RNA catalysts might have played a part in prebiotic nucleic acid replication, prior to the availability of useful proteins, if the RNA enzyme could use another copy of itself as a template, RNA self-replication could be achieved. Expand
Chemistry of potentially prebiological natural products
A relationship between what might be called a kinetic version of Le Chatelier's principle and chemical self-organization is considered. Some aspects of the search for a pre-RNA genetic system areExpand
Specific regulation of gene expression by antisense, sense and antigene nucleic acids.
The regula t ion of gene express ion in l iving organisms rests main ly upon the recogni t ion of nucleic acid base sequences by pro te ins [1,2]. However , nucleic acids can also p lay a role.Expand