A DNA‐Based Machine That Can Cyclically Bind and Release Thrombin

Dittmer, Wendy U.; Reuter, Andreas; Simmel, Friedrich C.

doi:10.1002/anie.200353537

Cited by 252 publications

(146 citation statements)

References 23 publications

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“…By taking advantage of the high versatility and designability of DNA chemistry [9][10][11][12][13][14][15][16][17][18][19] several groups have recently developed pH-triggered DNA-based probes or nanomachines [20][21][22][23][24][25][26][27][28][29][30] . Such probes typically exploit DNA secondary structures that display pH-dependence due to the presence of specific protonation sites.…”

Section: Introductionmentioning

confidence: 99%

Programmable pH-Triggered DNA Nanoswitches

2014

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ABSTRACT:Here we have rationally designed a tunable DNA-based nanoswitch whose closing/opening can be triggered over specific different pH windows. This nanoswitch forms an intramolecular triplex DNA structure through pH-sensitive parallel Hoogsteen interactions. We demonstrate that by simply changing the relative content of TAT/CGC triplets in the switch we can rationally tune its pH-dependence over more than 5 pH units. By using a combination of such nanowitches with different pH sensitivity, we also demonstrate how we can engineer a pH nanosensor that can precisely monitor pH variations over 5.5 units of pH. With their fast response time (<200 msec) and high reversibility, these pH-triggered nanoswitches appear particularly suitable for applications ranging from the real-time monitoring of pH changes in-vivo to the development of pH sensitive smart nanomaterial.Nature often employs finely pH-regulated biomolecules to modulate and tune a number of biological activities 1 ranging from enzyme catalysis 2 to protein folding 3 , membrane function 4 and apoptosis 5 . For these reasons, developing probes, switches or nanomaterials that are able to respond to specific pH changes should prove of utility for several applications in the fields of in-vivo imaging, clinical diagnostics, and drug-delivery [6][7][8] .By taking advantage of the high versatility and designability of DNA chemistry 9-19 several groups have recently developed pH-triggered DNA-based probes or nanomachines [20][21][22][23][24][25][26][27][28][29][30] . Such probes typically exploit DNA secondary structures that display pH-dependence due to the presence of specific protonation sites. These structures include I-motif [21][22][23]26,29,31 , intermolecular triplex DNA 25,28,32 , DNA tweezers 20 and, more recently, the Amotif 33 . Despite the promising and advantageous characteristics of some of these DNA-based nanomachines, which include fast response times and sustained efficiency over several cycles, a drawback inevitably affects their performances: they all respond (with an exception 33a ) over a fixed pH window that typically spans 1.5 to 2 pH units 26,34,33b . These nanomachines, therefore, cannot be adapted to provide a useful output outside these fixed pH-windows.Here we describe a method to rationally design and program pH-triggered DNA-based nanoswitches whose pH-dependence can be finely tuned and modulated over more than 5 units of pH. We created our switches by taking advantage of the wellcharacterized pH sensitivity of the parallel Hoogsteen (T,C)-motif in triplex DNA [34][35][36] . To do so we have designed a DNAbased triplex pH-triggered nanoswitch that consists in a double intramolecular hairpin stabilized with both Watson-Crick (W-C) and parallel Hoogsteen interactions (Fig. 1). More specifically, one hairpin of the triplex nanoswitch is formed by the W-C hybridization of two 10-base complementary portions separated by a 5 base loop. This duplex DNA is then able to form a triplex structure via the formation of a second hairpin through...

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Section: Introductionmentioning

confidence: 99%

Programmable pH-Triggered DNA Nanoswitches

2014

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“…As novel elements for molecular recognition, aptamers offer many advantages over protein antibodies, such as high affinity and specificity for target proteins, good stability, and ease of synthesis and modification (20 ). Aptamer-based analytical methods have been developed for protein-detection methods that use electrochemistry (21,22 ), fluorescence (23,24 ), and bindinginduced label-free detection (25 ).…”

confidence: 99%

Aptameric Molecular Switch for Cascade Signal Amplification

Zhao

et al. 2012

Clinical Chemistry

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“…The simplest devices, from the labs of Tan [34] and Mergny [35] are simple shape-shifting systems wherein a single-stranded G-quartet structure is eliminated by the addition of a molecule complementary to the strand; G-quartet-based devices are based on the notion that G-quartet-containing molecules are less stable than the same strands bound to their Watson-Crick complements. This approach has been developed by Simmel and colleagues [36] into a reversible thrombin-binding device. They.…”

Section: Non-watson-crick Base-paired Motifsmentioning

confidence: 99%

From genes to machines: DNA nanomechanical devices

Seeman

2005

Trends in Biochemical Sciences

342

213

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The structural properties that enable DNA to serve so effectively as genetic material can also be utilized for other purposes. The complementarity that leads to the pairing of the strands of the DNA double helix can be exploited to assemble more complex motifs, based on branched structures. These structures have been used as the basis of larger constructions in 2D and 3D. In addition, they have been used to make nanomechanical devices. These devices range from DNAbased shape-shifting structures to gears and walkers, a DNA stress-gauge, and even a translation device. The devices are activated by mechanisms as diverse as small molecules, proteins, and, most intriguingly, other molecules of DNA.

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A DNA‐Based Machine That Can Cyclically Bind and Release Thrombin

Cited by 252 publications

References 23 publications

Programmable pH-Triggered DNA Nanoswitches

Programmable pH-Triggered DNA Nanoswitches

Aptameric Molecular Switch for Cascade Signal Amplification

From genes to machines: DNA nanomechanical devices

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