Enhancement of TFO Triplex Formation by Conjugation with Pyrene &lt;i&gt;via&lt;/i&gt; Click Chemistry

Taniguchi, Yoshihiro; Tomizaki, Akira; Matsueda, Nozomu; Okamura, Hirokazu; Sasaki, Shigeki

doi:10.1248/cpb.c15-00570

Cited by 5 publications

(3 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…38,39) Substitution at the benzene unit of WNA-βT was able to partially solve the problem of sequence dependency. [40][41][42][43][44][45][46] To demonstrate the utility of WNA-βT for the antigene inhibition of gene expression, the WNA-βT was incorporated into amino-modified TFOs containing the promoter region of the Bcl2 and the survivin gene. 47) Bcl2 and survivin gene products are inhibitors of apoptosis and are overexpressed in a variety of tumors.…”

Section: Non-natural Nucleosides For the Formation Of Triplex Dna Anmentioning

confidence: 99%

Development of Novel Functional Molecules Targeting DNA and RNA

Sasaki

2019

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

Nucleic acid therapeutics such as antisense and small interfering RNA (siRNA) have attracted increasing attention as innovative medicines that interfere with and/or modify gene expression systems. We have developed new functional oligonucleotides that can target DNA and RNA with high efficiency and selectivity. This review summarizes our achievements, including (1) the formation of non-natural triplex DNA for sequencespecific inhibition of transcription; (2) artificial receptor molecules for 8-oxidized-guanosine nucleosides; and (3) reactive oligonucleotides with a cross-linking agent or a functionality-transfer nucleoside for RNA pinpoint modification.

show abstract

Section: Non-natural Nucleosides For the Formation Of Triplex Dna Anmentioning

confidence: 99%

Development of Novel Functional Molecules Targeting DNA and RNA

Sasaki

2019

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

show abstract

“…Development of agents for sequence-specific targeting of dsDNAs is an actual task of molecular biology and medicine, as the probes could become valuable tools for the regulation of the gene expression via inhibition of transcription, correction of mutations in DNA, and visualization of chromosomal DNA. To the moment, several promising approaches based on the use of simple agents as triplex-forming oligonucleotides (TFOs) [ 200 , 201 , 202 ], dsDNA Invader probes [ 17 ], PNAs [ 203 ], pseudocomplementary PNA [ 204 ], and minor groove-binding polyamides [ 205 ] as sequence-specific dsDNA binding probes have been suggested. Along with them, more sophisticated agents for dsDNA targeting, i.e., DNA-recognizing engineered peptides such as “zinc finger” nucleases based on DNA-binding domains of eukaryotic transcription factors, transcription activator-like effector nucleases (TALENs), and CRISPR/Cas9 systems are currently of special interest [ 206 , 207 , 208 ].…”

Section: Agents For Targeting Of Dsdnasmentioning

confidence: 99%

Recent Advances in Nucleic Acid Targeting Probes and Supramolecular Constructs Based on Pyrene-Modified Oligonucleotides

et al. 2017

View full text Add to dashboard Cite

In this review, we summarize the recent advances in the use of pyrene-modified oligonucleotides as a platform for functional nucleic acid-based constructs. Pyrene is of special interest for the development of nucleic acid-based tools due to its unique fluorescent properties (sensitivity of fluorescence to the microenvironment, ability to form excimers and exciplexes, long fluorescence lifetime, high quantum yield), ability to intercalate into the nucleic acid duplex, to act as a π-π-stacking (including anchoring) moiety, and others. These properties of pyrene have been used to construct novel sensitive fluorescent probes for the sequence-specific detection of nucleic acids and the discrimination of single nucleotide polymorphisms (SNPs), aptamer-based biosensors, agents for binding of double-stranded DNAs, and building blocks for supramolecular complexes. Special attention is paid to the influence of the design of pyrene-modified oligonucleotides on their properties, i.e., the structure-function relationships. The perspectives for the applications of pyrene-modified oligonucleotides in biomolecular studies, diagnostics, and nanotechnology are discussed.

show abstract

“…To date, we have developed the artificial nucleoside analogues to form the nonnatural and antiparallel type triplex DNA for the duplex DNA containing the CG and TA base pair to expand the triplex recognition code. [7][8][9][10][11][12] However, improvement of the stability of the antiparallel type triplex DNA by an artificial nucleic acid is a still challenging issue.…”

mentioning

confidence: 99%

Stable and Selective Antiparallel Type Triplex DNA Formation by Targeting a GC Base Pair with the TFO Containing One <i>N</i><sup>2</sup>-Phenyl-2′-deoxyguanosine

Taniguchi

Miyazaki

Matsueda

et al. 2018

CHEMICAL & PHARMACEUTICAL BULLETIN

Self Cite

View full text Add to dashboard Cite

The antiparallel triplex DNA is formed by the interaction between purine-rich triplex forming oligonucleotides (TFOs) and the homo-purine region within a duplex DNA. The formation of such a structure with the genome DNA promises to control the gene expression in a living cell. In this study, in an attempt to enhance the stability of the triplex DNAs, we have designed the N 2 -arylated deoxyguanosine derivatives. Among these analogues, we found that the TFOs containing N 2 -phenyl-2′-deoxyguanosine (PhdG) showed a stable and selective triplex DNA formation with the GC base pair as compared to the natural dG/GC triplet. However, the multiple incorporation of PhdG into the TFOs hampered the stable triplex DNA, instead, showed a tendency to form a higher order structure. Therefore, we concluded that the stable and selective triplex DNA formation is expected by the replacement of dG by PhdG in the purine-rich TFO sequence. Key words N2 -arylated deoxyguanosine; triplex forming oligonucleotide; triplex DNA By forming the triplex DNA versus the duplex DNA, it is possible to control the gene expression, gene recombination, gene repair, etc. Therefore, the site specific and stable triplex DNA formation for the target duplex DNA is anticipated to become an important method for the gene targeting technologies and therapies as an antigene method.1-5) The triplex DNA is formed by the interaction between the triplex forming oligonucleotides (TFOs) and the homopurine region within the duplex DNA.6) Triplex DNAs are classified into two types according to the orientation of the phosphate backbone of the TFOs. The antiparallel type triplex DNA is formed under neutral conditions, in which the TFOs composed of deoxyguanosine (dG) and deoxyadenosine (dA) form two hydrogen bonds in the guanine base of the GC base pair and the adenine base of the AT base pair of the duplex DNA, respectively, in an antiparallel orientation regarding the homopurine strand of the duplex DNA (Fig. 1A). On the other hand, the TFOs composed of deoxycytosine (dC) and thymidine (T) forms two hydrogen bond in the guanine base and adenine base of the homopurine strand in a parallel orientation, respectively. As the protonated cytidine is included in the parallel type triplex, its formation requires acidic conditions (Fig. 1B). To date, we have developed the artificial nucleoside analogues to form the nonnatural and antiparallel type triplex DNA for the duplex DNA containing the CG and TA base pair to expand the triplex recognition code.7-12) However, improvement of the stability of the antiparallel type triplex DNA by an artificial nucleic acid is a still challenging issue.The stacking interaction has been shown to be more effective with the triplex DNA than with the duplex DNA. For example, adriamycin and actinomycin, having a high aromaticity, are known to interact with the duplex DNA, but have a rather high binding ability to the triplex DNA.13) Moreover, the duplex DNA containing N 2 -phenyldeoxyguanosine (PhdG) showed a slightly higher thermal melting temp...

show abstract

Enhancement of TFO Triplex Formation by Conjugation with Pyrene <i>via</i> Click Chemistry

Cited by 5 publications

References 31 publications

Development of Novel Functional Molecules Targeting DNA and RNA

Development of Novel Functional Molecules Targeting DNA and RNA

Recent Advances in Nucleic Acid Targeting Probes and Supramolecular Constructs Based on Pyrene-Modified Oligonucleotides

Stable and Selective Antiparallel Type Triplex DNA Formation by Targeting a GC Base Pair with the TFO Containing One <i>N</i><sup>2</sup>-Phenyl-2′-deoxyguanosine

Contact Info

Product

Resources

About