Reduction‐Responsive Guanine Incorporated into G‐Quadruplex‐Forming DNA

Ikeda, Masato; Kamimura, Masahiro; Hayakawa, Yukihiro; Shibata, Aya; Kitade, Yukio

doi:10.1002/cbic.201600164

Cited by 17 publications

(20 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 61 ] Ikeda and coworkers recently incorporated a 4‐nitrobenzyl moiety at the O6 position of guanosine (G NB ) as a reduction‐responsive group that can be removed in response to both chemical (sodium hydrosulfite) and enzymatic (nitroreductase in the presence of NADH) stimuli. [ 62 ] This modification blocks Watson–Crick base‐pairing of the sequence containing the modification. The authors incorporated G NB into a thrombin‐binding aptamer (TBA), and showed that chemical reduction of the NB group was required for the aptamer to fold into its binding active G‐quadruplex state.…”

Section: Chemically Induced Switchingmentioning

confidence: 99%

Engineering Aptamer Switches for Multifunctional Stimulus‐Responsive Nanosystems

et al. 2020

View full text Add to dashboard Cite

specific and strong recognition of molecular targets (i.e., aptamers), catalyze biochemical reactions (i.e., ribozymes), or form sophisticated and dynamic "smart materials" or even 3D constructs (i.e., DNA origami). [2] There is particular interest in the use of nucleic acids for the construction of molecular switches, which undergo a function-altering structural change in response to an external stimulus. [3] Many such examples exist in nature, where switches enable organisms to sense physiological changes and selectively control biological functions in response. For example, riboswitches exist naturally as domains within messenger RNA (mRNA) transcripts that can bind to specific metabolites with high specificity in order to stabilize a secondary structure that prevents subsequent translation. [4] Synthetic, engineered molecular switches based on nucleic acids can achieve even greater diversity of function. Such designs make use of aptamersnucleic acid-based affinity reagents isolated via an in vitro process of systematic evolution by exponential enrichment (SELEX), in which DNA or RNA sequences with specific ligand binding are isolated from a large pool of random sequences. [5] Aptamers have proven to be robust recognition elements due to their thermal stability, ease of synthesis, and capacity to undergo ready modification with a broad array of functional groups. Importantly, traditional selection methods can be expanded upon by innovative engineering techniques to enable the incorporation of additional functions that further extend the utility of aptamers. Aptamers can adopt various 2-and 3-D structures such as duplexes, hairpins, and G-quadruplexes, and the inducible formation and disruption of these configurations can be exploited to enable complex functions besides simple biosensing. Consequently, aptamers have been incorporated into many intricate configurations, such as logic gates and dynamic nanomachines. Various research groups have also described aptamer-based switches that undergo conformational changes in response to triggers such as shifts in pH, stimulation with light, or the presence of a specific ligand. [6] Although still a relatively young area of research, these efforts could prove highly useful for materials research-conferring even greater and more selective control over devices based on functionalized nucleic acids. Aptamers are becoming increasingly integrated with various organic and inorganic molecules in order to control the assembly and operation of novel functional Although RNA and DNA are best known for their capacity to encode biological information, it has become increasingly clear over the past few decades that these biomolecules are also capable of performing other complex functions, such as molecular recognition (e.g., aptamers) and catalysis (e.g., ribozymes). Building on these foundations, researchers have begun to exploit the predictable base-pairing properties of RNA and DNA in order to utilize nucleic acids as functional materials that can undergo a molecular "switching" ...

show abstract

Section: Chemically Induced Switchingmentioning

confidence: 99%

Engineering Aptamer Switches for Multifunctional Stimulus‐Responsive Nanosystems

et al. 2020

View full text Add to dashboard Cite

show abstract

“…A nitrobenzyl (NB) group has also been introduced at O6 of a guanine to modulate the conformational properties of a G-quadruplex structure-forming single-stranded DNA [ 28 ]. The dG NB phosphoramidite was synthesized and incorporated into the sequence of a thrombin-binding DNA aptamer (TBA, at the 5’-end) prone to form a G-quadruplex structure ( Scheme 7 ).…”

Section: Reviewmentioning

confidence: 99%

“… Incorporation of O 6 -(4-nitrobenzyl)-2’-deoxyguanosine into an ON prone to form a G-quadruplex structure, preventing it from forming this quadruplex when protected and allowing it under reducing conditions [ 28 ]. …”

Section: Reviewmentioning

confidence: 99%

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

Debart¹,

Dupouy²,

Vasseur³

2018

Beilstein J. Org. Chem.

View full text Add to dashboard Cite

Oligonucleotides (ONs) have been envisaged for therapeutic applications for more than thirty years. However, their broad use requires overcoming several hurdles such as instability in biological fluids, low cell penetration, limited tissue distribution, and off-target effects. With this aim, many chemical modifications have been introduced into ONs definitively as a means of modifying and better improving their properties as gene silencing agents and some of them have been successful. Moreover, in the search for an alternative way to make efficient ON-based drugs, the general concept of prodrugs was applied to the oligonucleotide field. A prodrug is defined as a compound that undergoes transformations in vivo to yield the parent active drug under different stimuli. The interest in stimuli-responsive ONs for gene silencing functions has been notable in recent years. The ON prodrug strategies usually help to overcome limitations of natural ONs due to their low metabolic stability and poor delivery. Nevertheless, compared to permanent ON modifications, transient modifications in prodrugs offer the opportunity to regulate ON activity as a function of stimuli acting as switches. Generally, the ON prodrug is not active until it is triggered to release an unmodified ON. However, as it will be described in some examples, the opposite effect can be sought.This review examines ON modifications in response to various stimuli. These stimuli may be internal or external to the cell, chemical (glutathione), biochemical (enzymes), or physical (heat, light). For each stimulus, the discussion has been separated into sections corresponding to the site of the modification in the nucleotide: the internucleosidic phosphate, the nucleobase, the sugar or the extremities of ONs. Moreover, the review provides a current and detailed account of stimuli-responsive ONs with the main goal of gene silencing. However, for some stimuli-responsive ONs reported in this review, no application for controlling gene expression has been shown, but a certain potential in this field could be demonstrated. Additionally, other applications in different domains have been mentioned to extend the interest in such molecules.

show abstract

“…6 In a similar way, our group has recently developed O 6 -(4-nitrobenzyl)-modified guanosine (G NB , Figure 1B, a(iii)), which was incorporated into a Gquadruplex-forming DNA aptamer (15-mer). 7,8 It was demonstrated that both chemical and enzymatic reduction successfully trigger G-quadruplex formation ( Figure 2B). 7 Since the target protein binding function of such aptamers necessitates a secondary structure, such as a G-quadruplex, it is reasonably expected that the ability of the chemically caged aptamer to bind to its target protein can be controlled by reductive stimuli or environments in an OffOn manner.…”

Section: Introduction Sites For Responsive Unitsmentioning

confidence: 98%

“…7,8 It was demonstrated that both chemical and enzymatic reduction successfully trigger G-quadruplex formation ( Figure 2B). 7 Since the target protein binding function of such aptamers necessitates a secondary structure, such as a G-quadruplex, it is reasonably expected that the ability of the chemically caged aptamer to bind to its target protein can be controlled by reductive stimuli or environments in an OffOn manner. Saneyoshi et al developed O 4 -(4-nitrobenzyl)-modified thymine (T NB , Figure 1B, a(iv)) and introduced it into DNA 13-mers.…”

Section: Introduction Sites For Responsive Unitsmentioning

confidence: 98%

Chemically Caged Nucleic Acids

Ikeda

Kabumoto

2017

Chem. Lett.

Self Cite

View full text Add to dashboard Cite

Chemically caged nucleic acids, which comprise a nucleic acid moiety and a synthetic molecular moiety (or "responsive unit") that may be removed by an appropriate chemical stimulus, are valuable for the development of nucleic acid-based therapeutic strategies like prodrugs and medicine delivery systems. Light is one such stimulus, and excellent examples of photocaged nucleic acids have been developed. However, external light sources must be used for this methodology, and this presents problems concerning light penetration and off-target cytotoxicity. In contrast, chemically caged nucleic acids, which respond to chemical stimuli and autonomously modulate their functions without the need for external stimuli, present an alternative strategy for bioapplications. Herein, recent examples of chemically caged nucleic acids are presented, and the current limitations and future challenges encountered in this field are discussed.

show abstract

Reduction‐Responsive Guanine Incorporated into G‐Quadruplex‐Forming DNA

Cited by 17 publications

References 36 publications

Engineering Aptamer Switches for Multifunctional Stimulus‐Responsive Nanosystems

Engineering Aptamer Switches for Multifunctional Stimulus‐Responsive Nanosystems

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

Chemically Caged Nucleic Acids

Contact Info

Product

Resources

About