Template‐Assembled Synthetic G‐Quartets (TASQs)

Nikan, Mehran; Sherman, John C.

doi:10.1002/ange.200704199

Cited by 20 publications

(3 citation statements)

References 40 publications

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“…higher-order structures made of successive quadruplex units that result from the folding of long G-rich telomeric fragments) (24). In the course of our study, we found a way to improve the DNAzyme activities of both monomeric and multimeric quadruplexes by the use of a synthetic G-quartet (known as TASQ, for Template-Assembled Synthetic G-Quartet) (25,26), namely DOTASQ [for DOTA-templated Synthetic G-Quartet (27)]: the concomitant use of DNA and DOTASQ enables the hemin to be sandwiched at both extremities of quadruplex architectures, thereby being in a pocket whose hydrophobicity is optimal for catalyzing efficiently the peroxidatic process. The boosting effect of DOTASQ was efficient but modest (up to 6-fold) and enabled to lower the limit for reliable DNA detection at ∼500 nM scale.…”

Section: Introductionmentioning

confidence: 99%

Insights into how nucleotide supplements enhance the peroxidase-mimicking DNAzyme activity of the G-quadruplex/hemin system

Stefan

Denat

Monchaud

2012

Nucleic Acids Research

145

154

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Since the initial discovery of the catalytic capability of short DNA fragments, this peculiar enzyme-like property (termed DNAzyme) has continued to garner much interest in the scientific community because of the virtually unlimited applications in developing new molecular devices. Alongside the exponential rise in the number of DNAzyme applications in the last past years, the search for convenient ways to improve its overall efficiency has only started to emerge. Credence has been lent to this strategy by the recent demonstration that the quadruplex-based DNAzyme proficiency can be enhanced by ATP supplements. Herein, we have made a further leap along this path, trying first of all to decipher the actual DNAzyme catalytic cycle (to gain insights into the steps ATP may influence), and subsequently investigating in detail the influence of all the parameters that govern the catalytic efficiency. We have extended this study to other nucleotides and quadruplexes, thus demonstrating the versatility and broad applicability of such an approach. The defined exquisitely efficient DNAzyme protocols were exploited to highlight the enticing advantages of this method via a 96-well plate experiment that enables the detection of nanomolar DNA concentrations in real-time with the naked-eye (see movie as Supplementary Data).

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Section: Introductionmentioning

confidence: 99%

Insights into how nucleotide supplements enhance the peroxidase-mimicking DNAzyme activity of the G-quadruplex/hemin system

Stefan

Denat

Monchaud

2012

Nucleic Acids Research

145

154

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“…Keywords: DNA recognition · Gquadruplexes · heterocycles · ligand design · polycycles currently the focus of intense attention with the aim to decipher their biological roles [6] and to evaluate their potential for building DNA-based nanoobjects. [7] Interestingly, quadruplexes may bind small molecules, which in turn stabilize these structures and may act as molecular silencers by shifting a functional DNA conformation (duplex) to a nonfunctional one (quadruplex). Over the past decade, the search for small molecules acting as quadruplex ligands has developed dramatically with essentially two major goals: finding probes to sense quadruplex formation in various biological contexts and discovering new DNA-interacting agents of potential therapeutic interest.…”

Section: Introductionmentioning

confidence: 99%

Recognition of G‐Quadruplex DNA by Triangular Star‐Shaped Compounds: With or Without Side Chains?

Bertrand

Granzhan

Monchaud

et al. 2011

Chemistry A European J

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We report the synthesis of two new series of triangular aromatic platforms, either with three aminoalkyl side chains (triazatrinaphthylene series, TrisK: six compounds), or without side chains (triazoniatrinaphthylene, TrisQ). The quadruplex-DNA binding behavior of the two series, which differ essentially by the localization of the cationic charges, was evaluated by means of FRET-melting and G4-FID assays. For the trisubstituted triazatrinaphthylenes (TrisK), the length of the substituents and the presence of terminal hydrogen-bond-donor groups (NH(2)) were shown to be crucial for ensuring a high quadruplex affinity (ΔT(1/2) values of up to 20 °C at 1 μM for the best candidate, TrisK3-NH) and selectivity versus duplex DNA. Subsequently, comparison of data collected on both the telomeric- and c-myc-quadruplex showed that the nonsubstituted TrisQ is even more efficient than TrisK3-NH, both in terms of quadruplex affinity (ΔT(1/2)=26 °C in K(+) buffer) and selectivity versus duplex DNA. Structural considerations conducted with the c-myc quadruplex indicate that both TrisK3-NH and TrisQ stack well onto the G-quartet but in an offset position, which might be influenced by the formation of multiple hydrogen bonds with the target in the former case. Finally, the nonsubstituted TrisQ displays a binding profile very similar to some of the best quadruplex binders, BRACO-19 and bisquinolinium 360A, used herein as references, and thereby represents a highly promising novel molecular design for quadruplex recognition.

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“…Despite a large number of examples that use this template, to our knowledge, it has not been applied for the design of a specific folded structure of nucleic acid. [11] With this in mind, we investigated the use of a peptidic scaffold as a topological template that directs the intramolecular assembly of covalently attached oligonucleotides into a single characteristic folding topology of G quadruplex. We anticipated that the scaffold should permit the preorganization of the DNA strands and the stabilization of the quadruplex structure.…”

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confidence: 99%