2′-O-Dimethylaminoethoxyuridine and 5-Dimethylaminopropargyl Deoxyuridine for at Base Pair Recognition in Triple Helices

Brennan, Lavinia; Peng, Guomei; Srinivasan, Natarajan; Fox, Keith R.; Brown, Tom

doi:10.1080/15257770701530525

Cited by 6 publications

(4 citation statements)

References 8 publications

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“…The phosphoramidite monomers for the analogues were synthesized as previously reported ( 15 , 22 ). The synthesis of the phosphoramidite of 5-guanidinopropargyl-dU is described in the supplementary material .…”

Section: Methodsmentioning

confidence: 99%

“…We have previously reported the synthesis of the nucleoside analogue 5-dimethylaminopropargyl deoxyuridine (DMAPdU; Figure 1 A) ( 22 ). This analogue is similar to 5-aminopropargyl dU (APdU) but contains a dimethylamine in place of the primary amine at the 5-position.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast to a primary amine, DMAPdU does not require protection during phosphoramidite monomer or oligonucleotide synthesis. Preliminary melting experiments have shown that although DMAPdU is not as stabilizing as APdU against an AT base pair it does lead to enhanced triplex stability ( 22 ). Here we further explore the sequence selectivity and affinity of this analogue by examining TFOs that contain single or multiple substitutions of the analogue at different positions within the TFO.…”

Section: Introductionmentioning

confidence: 99%

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DNA triplex formation with 5-dimethylaminopropargyl deoxyuridine

Rusling

Peng

Srinivasan

et al. 2009

Nucleic Acids Research

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We have prepared triplex-forming oligonucleotides containing the nucleotide analogue 5-dimethylaminopropargyl deoxyuridine (DMAPdU) in place of thymidine and examined their ability to form intermolecular triple helices by thermal melting and DNase I footprinting studies. The results were compared with those for oligonucleotides containing 5-aminopropargyl-dU (APdU), 5-guanidinopropargyl-dU (GPdU) and 5-propynyl dU (PdU). We find that DMAPdU enhances triplex stability relative to T, though slightly less than the other analogues that bear positive charges (T << PdU < DMAPdU < APdU < GPdU). For oligonucleotides that contain multiple substitutions with DMAPdU dispersed residues are more effective than clustered combinations. DMAPdU will be especially useful as a nucleotide analogue as, unlike APdU and GPdU, the base does not require protection during oligonucleotide synthesis and it can therefore be used with other derivatives that require mild deprotection conditions.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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DNA triplex formation with 5-dimethylaminopropargyl deoxyuridine

Rusling

Peng

Srinivasan

et al. 2009

Nucleic Acids Research

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“…An approach different for increasing triplex stability is to modify the TAT triplet. Few efforts have been made to improve the stability of TAT triplet [32][33][34][35][36][37][38][39][40][41] . Experiments with 5-propargylamino-dU as a charged analogue of thymine to stabilize TAT triplet have been described 35 .…”

Section: Introductionmentioning

confidence: 99%

Oligodeoxynucleotide Containing Disulphide Bond Stabilizes Triplex DNA Structure

Kumar

2010

Journal of Chemistry

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The triplex formation of disulphide containing oligonucleotide with duplex DNA using melting temperature studies is reported. The stability of the triplex formed with disulphide containing oligonucleotide was compared with unmodified oligonucleotide and C-5 propyne deoxyuridine containing oligonucleotide. Melting temperature (Tm) values of the triplexes formed with disulphide containing oligonucleotide were found to be 37°C and 46°C at pH 7 and 6 respectively. The triplexes formed with C-5 propyne deoxyuridine substituted oligonucleotide showed Tmvalues at 27°C and 42°C at pH 7 and 6. The Tmvalues of the triplexes formed with unmodified oligonucleotide were found to be 18°C and 32°C at pH 7 and 6 respectively. This clearly demonstrates that disulphide containing oligonucleotide stabilzes triplex DNA structure better than unmodified oligonucleotide as well as C-5 propyne deoxyuridine containing oligonucleotide when targeted with duplex DNA at both the mentioned pH values.

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Cross-linking to an interrupted polypurine sequence with a platinum-modified triplex-forming oligonucleotide

Campbell

Miller

2009

J Biol Inorg Chem

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Triplex-forming oligonucleotides (TFOs) can bind specifically to polypurine sequences in doublestranded DNA. A single interruption of this polypurine tract can greatly destabilize triplex formation. The stability of triplexes can be significantly enhanced by covalently linking the TFO to its DNA target with reactive functional groups conjugated to the TFO. Covalently cross-linked TFOs are effective inhibitors of transcription of the target DNA sequence. We have designed a TFO with a platinum-modified base that can interact with and cross-link to a cytosine interruption in the polypurine tract of a target DNA duplex. The TFO contains an N 4 -(aminoalkyl)cytosine derivatized with cis-or trans-diamminediaquaplatinum(II). When bound to its target, the tethered platinum of the TFO can reach across the major groove and form an adduct with the guanine N7 of the interrupting C·G base-pair. The optimal tether length is five methylene groups, and cross-linking is most efficient when the tether is modified with trans-diamminediaquaplatinum. Cross-linking requires that the TFO is bound to its designated DNA target. Addition of cyanide to the cross-linked TFO product reversed the cross-link, behavior that is consistent with the presence of a Pt-guanine adduct. The kinetics of the cross-linking reaction were studied and the half-life of the cross-linking reaction was approximately three hours. Our results demonstrate that platinum-conjugated TFOs can be designed to cross-link with DNA targets that contain a single pyrimidine interruption. Modifications of this type may prove useful for expanding the DNA sequences that can be targeted by TFOs and increasing the stability of the resulting triplexes.

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2′-O-Dimethylaminoethoxyuridine and 5-Dimethylaminopropargyl Deoxyuridine for at Base Pair Recognition in Triple Helices

Abstract: The nucleoside analogues 2'-O-dimethylaminoethoxy uridine and 5-dimethylaminopropargyl deoxyuridine have been synthesised and incorporated into oligonucleotides. Their triplex-stabilising properties have been determined in fluorescence melting experiments.

Cited by 6 publications

References 8 publications

DNA triplex formation with 5-dimethylaminopropargyl deoxyuridine

DNA triplex formation with 5-dimethylaminopropargyl deoxyuridine

Oligodeoxynucleotide Containing Disulphide Bond Stabilizes Triplex DNA Structure

Cross-linking to an interrupted polypurine sequence with a platinum-modified triplex-forming oligonucleotide

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