New junction models for alternate-strand triple-helix formation
Identifieur interne : 000274 ( France/Analysis ); précédent : 000273; suivant : 000275New junction models for alternate-strand triple-helix formation
Auteurs : Thérèse De Bizemont [France] ; Jian-Sheng Sun [France] ; Thérèse Garestier [France] ; Claude Hélène [France]Source :
- Chemistry & Biology [ 1074-5521 ] ; 1998.
English descriptors
- Teeft :
- Additional cytosines, Additional stabilization, Alternate strand, Antiparallel, Base pair, Base pair fragment, Base pair fragments, Base quadruplets, Base triplet, Base triplets, Bizemont, Chemistry biology, Chloroacetaldehyde, Clear footprint, Cytosine, Dnase, Double helix, Duplex, Energy minimization, Footprinting, Footprinting experiments, Formic acid, Groove, Guanine, Helix, Hoogsteen, Hoogsteen base triplets, Hoogsteen configuration, Hoogsteen part, Hoogsteen portion, Hoogsteen side, Junction, Junction step, Junctions bizemont, Major groove, Minimization, Modeling, Molecular modeling, Nucleic, Nucleic acids, Nucleotide, Oligonucleotide, Oligonucleotides, Oligopurine, Oligopurine sequences, Opposite orientations, Quadruplet, Strand, Third strand, Thymine, Triple helices, Triple helix formation, Triplet, Triplex, Triplex formation.
Abstract
Abstract: Background: Oligonucleotide-directed triple-helix (triplex) formation can interfere with gene expression but only long tracts of oligopyrimidine·oligopurine sequences can be targeted. Attempts have been made to recognize short oligopurine sequences alternating on the two strands of double-stranded DNA by the covalent linkage of two triplex-forming oligonucleotides. Here we focus on the rational optimization of such an alternate-strand triplex formation on a DNA duplex containing a 5′-GpT-3′/3′-CpA-5′ or a 5′-TpG-3′/3′-ApC-5′ step by combination of (G,T)- and (G,A)-contain ing oligonucleotides that bind to the oligopurine strands in opposite orientations. Results: The deletion of one nucleotide in the reverse Hoogsteen region of the oligonucleotide provides the best binding at the 5′-GpT-3′/3′-CpA-5′ step, whereas the addition of two cytosines as a linker between the two oligonucleotides is the best strategy to cross a 5′-TpG-3′/3′-ApC-5′ step. Energy minimization and experimental data suggest that these two cytosines are involved in the formation of two novel base quadruplets. Conclusions: These data provide a rational basis for the design of oligonucleotides capable of binding to oligopurine sequences that alternate on the two strands of double-stranded DNA with a 5′-GpT-3′/3′-CpA-5′ or a 5′-TpG-3′/3′-ApC-5' step at the junction.
Url:
DOI: 10.1016/S1074-5521(98)90667-6
Affiliations:
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<term>Groove</term>
<term>Guanine</term>
<term>Helix</term>
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<term>Hoogsteen base triplets</term>
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<term>Hoogsteen portion</term>
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<term>Junctions bizemont</term>
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<term>Minimization</term>
<term>Modeling</term>
<term>Molecular modeling</term>
<term>Nucleic</term>
<term>Nucleic acids</term>
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<term>Oligonucleotide</term>
<term>Oligonucleotides</term>
<term>Oligopurine</term>
<term>Oligopurine sequences</term>
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<term>Quadruplet</term>
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<term>Third strand</term>
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<front><div type="abstract" xml:lang="en">Abstract: Background: Oligonucleotide-directed triple-helix (triplex) formation can interfere with gene expression but only long tracts of oligopyrimidine·oligopurine sequences can be targeted. Attempts have been made to recognize short oligopurine sequences alternating on the two strands of double-stranded DNA by the covalent linkage of two triplex-forming oligonucleotides. Here we focus on the rational optimization of such an alternate-strand triplex formation on a DNA duplex containing a 5′-GpT-3′/3′-CpA-5′ or a 5′-TpG-3′/3′-ApC-5′ step by combination of (G,T)- and (G,A)-contain ing oligonucleotides that bind to the oligopurine strands in opposite orientations. Results: The deletion of one nucleotide in the reverse Hoogsteen region of the oligonucleotide provides the best binding at the 5′-GpT-3′/3′-CpA-5′ step, whereas the addition of two cytosines as a linker between the two oligonucleotides is the best strategy to cross a 5′-TpG-3′/3′-ApC-5′ step. Energy minimization and experimental data suggest that these two cytosines are involved in the formation of two novel base quadruplets. Conclusions: These data provide a rational basis for the design of oligonucleotides capable of binding to oligopurine sequences that alternate on the two strands of double-stranded DNA with a 5′-GpT-3′/3′-CpA-5′ or a 5′-TpG-3′/3′-ApC-5' step at the junction.</div>
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