A-tract DNA disfavours triplex formation. Sandström, K., Wärmländer, S., Gräslund, A., & Leijon, M. Journal of molecular biology, 315(4):737–48, January, 2002. ![A-tract DNA disfavours triplex formation. [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Optimisation of DNA triplex stability is of fundamental importance in the anti-gene strategy. In the present work, thermal denaturation studies by UV-spectrophotometry and structural and dynamical characterizations by NMR spectroscopy have been used systematically to investigate the effects on triplex stability of isolated insertions of different base triplets into an otherwise homogeneous 15-mer dT x dA-dT oligo-triplex. 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. To a smaller degree, this is the case also for a C(+) x I-C triplet insertion. Using imino proton exchange measurements, it is shown that insertion of a DT base-pair in the underlying duplex perturbs the intrinsic A-tract structure in the same way as has been shown for a GC insert. We propose that the intrinsic properties of A-tract duplex DNA (e. g. high propeller twist and rigidity) are unfavourable for triplex formation and that GC- or DT-inserts stabilize the triplex by interfering with the A-tract features of the underlying duplex. The C(+) x I-C triplet without the N2 amino group in the minor groove is readily accommodated within the typical, highly propeller-twisted A-tract structure. This might be related to its smaller effect on the stability of the corresponding triplex. These results may be valuable for understanding DNA triplex formation in vivo as well as for the design of efficient triplex-forming oligonucleotides and in choosing suitable target sequences in the anti-gene strategy.
@article{sandstrom_-tract_2002,
title = {A-tract {DNA} disfavours triplex formation.},
volume = {315},
issn = {0022-2836},
url = {http://www.ncbi.nlm.nih.gov/pubmed/11812143},
doi = {10.1006/jmbi.2001.5249},
abstract = {Optimisation of DNA triplex stability is of fundamental importance in the anti-gene strategy. In the present work, thermal denaturation studies by UV-spectrophotometry and structural and dynamical characterizations by NMR spectroscopy have been used systematically to investigate the effects on triplex stability of isolated insertions of different base triplets into an otherwise homogeneous 15-mer dT x dA-dT oligo-triplex. 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. To a smaller degree, this is the case also for a C(+) x I-C triplet insertion. Using imino proton exchange measurements, it is shown that insertion of a DT base-pair in the underlying duplex perturbs the intrinsic A-tract structure in the same way as has been shown for a GC insert. We propose that the intrinsic properties of A-tract duplex DNA (e. g. high propeller twist and rigidity) are unfavourable for triplex formation and that GC- or DT-inserts stabilize the triplex by interfering with the A-tract features of the underlying duplex. The C(+) x I-C triplet without the N2 amino group in the minor groove is readily accommodated within the typical, highly propeller-twisted A-tract structure. This might be related to its smaller effect on the stability of the corresponding triplex. These results may be valuable for understanding DNA triplex formation in vivo as well as for the design of efficient triplex-forming oligonucleotides and in choosing suitable target sequences in the anti-gene strategy.},
number = {4},
journal = {Journal of molecular biology},
author = {Sandström, Karin and Wärmländer, Sebastian and Gräslund, Astrid and Leijon, Mikael},
month = jan,
year = {2002},
pmid = {11812143},
keywords = {\#nosource, Base Composition, Base Pairing, Base Pairing: drug effects, Base Sequence, DNA, DNA: chemistry, DNA: genetics, DNA: metabolism, Kinetics, Magnesium Chloride, Magnesium Chloride: pharmacology, Magnetic Resonance Spectroscopy, Mutation, Mutation: genetics, Nucleic Acid Conformation, Nucleic Acid Conformation: drug effects, Nucleic Acid Denaturation, Nucleic Acid Denaturation: drug effects, Poly A, Poly A: genetics, Sodium Chloride, Sodium Chloride: pharmacology, Spectrophotometry, Structure-Activity Relationship, Temperature, Ultraviolet},
pages = {737--48},
}
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C if the cytosine base is C5 methylated) at acidic as well as neutral pH. To a smaller degree, this is the case also for a C(+) x I-C triplet insertion. Using imino proton exchange measurements, it is shown that insertion of a DT base-pair in the underlying duplex perturbs the intrinsic A-tract structure in the same way as has been shown for a GC insert. We propose that the intrinsic properties of A-tract duplex DNA (e. g. high propeller twist and rigidity) are unfavourable for triplex formation and that GC- or DT-inserts stabilize the triplex by interfering with the A-tract features of the underlying duplex. The C(+) x I-C triplet without the N2 amino group in the minor groove is readily accommodated within the typical, highly propeller-twisted A-tract structure. This might be related to its smaller effect on the stability of the corresponding triplex. 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