The effect of amino groups on the stability of DNA duplexes and triplexes based on purines derived from inosine.

  title={The effect of amino groups on the stability of DNA duplexes and triplexes based on purines derived from inosine.},
  author={Elena Cubero and R G{\"u}imil-Garc{\'i}a and Francisco Javier Luque and Ram{\'o}n Eritja and Modesto Orozco},
  journal={Nucleic acids research},
  volume={29 12},
The effect of amino groups attached at positions 2 and 8 of the hypoxanthine moiety in the structure, reactivity and stability of DNA duplexes and triplexes is studied by means of quantum mechanical calculations, as well as extended molecular dynamics (MD) and thermodynamic integration (MD/TI) simulations. Theoretical estimates of the change in stability related to 2'-deoxyguanosine (G) --> 2'-deoxyinosine (I) --> 8-amino-2'-deoxyinosine (8AI) mutations have been experimentally verified, after… 

Structural Properties of G,T-Parallel Duplexes

The preference for the parallel-duplex over the Watson-Crick antiparallel duplex is attributed to the strong stabilization of the parallel duplex produced by the 8-aminopurines.

Dynamics and Stability of GCAA Tetraloops with 2-Aminopurine and Purine Substitutions

The theoretical estimates suggest a larger destabilization for the G to AP substitutions in GCAA loop than for the substitutions of individual A's by PUR, which is in accordance with experimental tendency.

Recombination R-triplex: H-bonds contribution to stability as revealed with minor base substitutions for adenine

The enthalpy of the 10 nt long intramolecular triplex of −100 kJ·mol−1 demonstrates that the R-triplex is relatively unstable and thus an ideal candidate for a transient intermediate in homologous recombination, t-loop formation at the mammalian telomere ends, and short RNA invasion into a duplex.

A-tract DNA disfavours triplex formation.

It is found that insertion of a single central C(+) x G-C or T x D-T triplet (D=2,6-diaminopurine) leads to a pronounced stabilization (up to 20 deg. C if the cytosine base is C5 methylated) at acidic as well as neutral pH.

A computational characterization of the hydrogen-bonding and stacking interactions of hypoxanthine.

Although the calculations support suggestions from experiments that hypoxanthine preferentially binds with cytosine, the trend in the calculated hydrogen-bond strengths for the remaining natural nucleobases do not show a strong correlation with the experimentally predicted binding preferences, and stacking interactions should also be considered when analyzing the stability of DNA helices containing hypoxantha.

Structure of triplex DNA in the gas phase.

Results argue against the generally assumed roles of the different physical interactions (solvent screening of phosphate repulsion, hydrophobic effect, and solvation of accessible polar groups) in modulating the stability of DNA structures.

Properties of triple helices formed by parallel-stranded hairpins containing 8-aminopurines.

Hairpins carrying 8-aminopurines give very stable triple helical structures even at neutral pH, as confirmed by gel-shift experiments, circular dichroism and nuclear magnetic resonance spectroscopy.

Effects of strand and directional asymmetry on base–base coupling and charge transfer in double-helical DNA

  • M. A. O'neillJ. Barton
  • Chemistry, Physics
    Proceedings of the National Academy of Sciences of the United States of America
  • 2002
Mechanistic models of charge transfer (CT) in macromolecules often focus on CT energetics and distance as the chief parameters governing CT rates and efficiencies. However, in DNA, features unique to

Dynamical treatment of charge transfer through duplex nucleic acids containing modified adenines.

It is argued that the electronic structure and charge transfer ability of flexible polymers is the result of a complex intertwining of various structural, dynamical and chemical factors.



Theoretical calculations, synthesis and base pairing properties of oligonucleotides containing 8-amino-2'-deoxyadenosine.

These calculations indicate a strong preferential stabilization of the triplex over the duplex when adenine is replaced by 8-aminoadenine, which could benefit biological applications of triple helices and very stable triple helical structures can be observed even at neutral pH.

The contribution of cytosine protonation to the stability of parallel DNA triple helices.

The very large stabilisation from protonation is too large to be accounted for by a single hydrogen bond, and is likely to include contributions from electrostatic interactions of the positive charge with the phosphate backbone, and more favourable interactions between neighbouring bases owing to the very different electronic properties of the protonated C.C+ triplets.

Triple helical structures involving inosine: there is a penalty for promiscuity.

This paper presents a series of oligonucleotides with a 5'pur9-pyr9- pyr9 motif which are designed to fold up sequentially into intramolecular triple helices, and concludes that under no circumstances does inosine replacement stabilize the triplex helix: it is a poor substitute and its role as a wild-card is limited.

Hydrophobic, Non-Hydrogen-Bonding Bases and Base Pairs in DNA.

The properties of hydrophobic isosteres of pyrimidines and purines in synthetic DNA duplexes are reported and the possibility of using these or related base pairs to expand the genetic code beyond the natural A-T and G-C pairs is raised.

Observation of Spontaneous Base Pair Breathing Events in the Molecular Dynamics Simulation of a Difluorotoluene-Containing DNA Oligonucleotide

Extended molecular dynamics (MD) and thermodynamic integration (MD-TI) calculations have been used to determine the structural and energetic changes in DNA that accompany the replacement of thymine

Solution structure of a pyrimidine-purine-pyrimidine triplex containing the sequence-specific intercalating non-natural base D3.

NMR spectroscopy is used to study a pyrimidine-purine-pyrimidine DNA triplex containing a non-natural base, 1-(2-deoxy-beta-D-ribofuranosyl)-4-(3-benzamido)phenylimidazole (D3), in the third strand and the conformation of the D3 base and its sequence specificity are discussed.

DNA-triplex stabilizing properties of 8-aminoguanine.

A DNA-triplex stabilizing purine (8-aminoguanine) is designed based on molecular modeling and synthesized and it is demonstrated that few changes are found in the structure of the triplex due to the presence of this modified base.

Electrostatic effects in DNA triple helices.

To investigate the extent of the local and global electrostatic effects further, two families of oligonucleotides have been synthesized and share as a common design feature that they all fold sequentially into isosterical intramolecular triple helices by way of hairpin intermediates.

Complexes formed by (pyrimidine)n . (purine)n DNAs on lowering the pH are three-stranded.

The present work is inconsistent with the view that this complex was thought to be tetra-stranded, and four lines of evidence show that the complex consists of a triplex together with a poly d(purine) possessing secondary structure.

Effect of 5-methylcytosine on the stability of triple-stranded DNA--a thermodynamic study.

It is concluded that cytosine methylation expands the pH range compatible with triplex formation by one pH unit and indicates that the extra stability imparted to the triplex by methylcytosine is entropic in origin.