Comparative circular dichroism and fluorescence studies of oligodeoxyribonucleotide and oligodeoxyribonucleoside methylphosphonate pyrimidine strands in duplex and triplex formation

Callahan, D.E.; Trapane, Tina L.; Miller, Paul S.; Ts’o, Paul O. P.; Kan, Lou Sing

doi:10.1021/bi00220a030

Cited by 80 publications

(47 citation statements)

References 24 publications

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“…In such a case, the observed induced CD signal at 315 nm simply may reflect the association of Net with the final duplex state. To assess this possibility, we examined the lower wavelength region of the CD spectra, since between 200 and 230 nm, duplex structures are characterized by a positive band whereas triplexes exhibit a negative band (21,22,(35)(36)(37)(38)(39)(40)(41). Inspection of the CD spectra in Fig.…”

Section: Resultsmentioning

confidence: 99%

Drug binding to higher ordered DNA structures: netropsin complexation with a nucleic acid triple helix.

Park

Breslauer

1992

Proc. Natl. Acad. Sci. U.S.A.

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We have used a combination of spectroscopic and calorimetric techniques to characterize how netropsin, a ligand that binds in the minor groove of DNA, influences the properties of a DNA triple helix. Specifically, our data allow us to reach the following conclusions: (i) netropsin binds to the triplex without displacing the major-groove-bound third strand; (ui) netropsin binding to the triplex exhibits a lower saturation binding density (7.0 base triplets per netropsin bound) than netropsin binding to the corresponding duplex (5.5 base pairs per netropsin bound); (iii) the netropsin-free and the netropsin-bound triplexes each melt in two well-resolved transitions, initial conversion of the triplex to the duplex state followed by duplex melting to the component single-stranded states; (iv) netropsin remains bound to DNA as the triplex melts to the duplex state; (v) netropsin binding thermally destabilizes the triplex = duplex equilibrium dramatically, while thermally stabilizing the duplex to single-strand equilibrium; (vi) netropsin binding to the triplex is enthalpically 4 times more favorable (more exothermic) than netropsin binding to the corresponding duplex; (vi) netropsin binding to the triplex decreases the cooperativity of the triplex --duplex melting event. These results demonstrate that occupancy of the minor groove of a triplex by a ligand such as netropsin can exert a profound impact on the properties of the host triplex, particularly with regard to the equilibrium in which the third strand is expelled from the major groove. Thus, our results reveal considerable major groove/minor groove crosstalk. Such knowledge may prove of practical importance by providing an approach for modulating the affinity and specificity of majorgroove-binding third strands in triplex-forming protocols designed to target specific duplex domains. Fundamentally, our results provide insights into the crosstalk that can result when ligands bind to the two major receptor sites of duplex DNAnamely, the major and minor grooves.Interest in triple helical DNA has been stimulated by the recognition of potential biological roles and/or applications for triple-stranded structures. For example, a structure called H-DNA, which includes a triple helical region, has been proposed to explain the enhanced sensitivity of polypurine-polypyrimidine sequences to chemical cutting agents and to single-strand-specific endonucleases (1-3). Triple strand formation also has been exploited to facilitate the delivery and to enhance the sequence specificity of DNA-cutting reagents (4-6) and drugs (7,8). In addition, triple strand formation has been used to modify enzyme cutting patterns by selectively blocking enzyme binding sites in the major groove (9, 10). In short, appropriately designed and constructed third-strand oligonucleotides that hybridize to targeted duplex domains can be used to control gene expression, to serve as artificial endonucleases in gene mapping strategies, to dictate or modulate the sequence specificity of DNA-binding ...

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Section: Resultsmentioning

confidence: 99%

Drug binding to higher ordered DNA structures: netropsin complexation with a nucleic acid triple helix.

Park

Breslauer

1992

Proc. Natl. Acad. Sci. U.S.A.

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“…For example, triple-helix formation 1 and the conversion of the right-handed duplex to left-handed Z-DNA 2 are ionic strength dependent processes. Perhaps more physiologically relevant is the observation that changes in the ionic environment induce conformation changes in histone proteins and in nucleosomes, the biochemically active macromolecular complexes of DNA.…”

Section: Introductionmentioning

confidence: 99%

Divalent cations and the electrostatic potential around DNA: Monte Carlo and Poisson-Boltzmann calculations

1999

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“…Binding results in the formation of hydrogen-bonded T.AT and C+.GC triplets in which pyrimidines in the thirdstrand are Hoogesteen-bound to the purines of the DNA duplex [1][2][3]. Several researclaers have used DNA triplexes including modified bases and phosphate groups on the third strand in order to develop highly selective drugs [4][5][6][7][8][9][10][11][12]. We report the effect of phosphorothioate substitution on the conformation of a triplex of DNA.…”

Section: Introductionmentioning

confidence: 99%

The influence of oligodeoxyribonucleotide phosphorothioate pyrimidine strands on triplex formation

et al. 1992

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Analogues of the homopyrimidine oiigonucleotide dT,s that contained phosphorothioat¢ bonds of a mixture ofdiastereoisomers or one of tile two stereoisomers (either Rp or Sp) were synthesized. The analogues were mixed under eondition~ conducive to the formation of tripl¢.-.atranded assemblies. The mixtures were characterized by their thermal stabilities (7"1,, values), CD spectra, and gel electropltoresis pattern. The 34-met duplexes containing 15 central purines on one strand attd 15 complementary pyrimidines on the other strand gave no detectable triple helix upon combination with dTt~S~. On the other hand, 34-bp duplexes with dT~sS,, having Rp or Sp, formed triple helix~. This suggests that a sterie factor plays an important role in triple helix formation.

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Comparative circular dichroism and fluorescence studies of oligodeoxyribonucleotide and oligodeoxyribonucleoside methylphosphonate pyrimidine strands in duplex and triplex formation

Cited by 80 publications

References 24 publications

Drug binding to higher ordered DNA structures: netropsin complexation with a nucleic acid triple helix.

Drug binding to higher ordered DNA structures: netropsin complexation with a nucleic acid triple helix.

Divalent cations and the electrostatic potential around DNA: Monte Carlo and Poisson-Boltzmann calculations

The influence of oligodeoxyribonucleotide phosphorothioate pyrimidine strands on triplex formation

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