A DNA Nanodevice That Loads and Releases a Cargo with Hemoglobin-Like Allosteric Control and Cooperativity

Mariottini, Davide; Idili, Andrea; Vallée‐Bélisle, Alexis; Plaxco, Kevin W.; Ricci, Francesco

doi:10.1021/acs.nanolett.7b00814

Cited by 33 publications

(26 citation statements)

References 51 publications

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“…Plaxco described how allostery and cooperativity may be leveraged to engineer a wide range of artificial optical, biochemical, and electrochemical biosensors. Among the examples used to illustrate the approach was the rational design and engineering of a synthetic DNA-based nanodevice containing up to four interacting binding sites that can load and release a cargo over narrow concentration ranges, and whose affinity could be finely controlled via both allosteric effectors and environmental cues such as pH and temperature (Mariottini et al, 2017). In another example, catalytic DNAzyme sequences (e.g., peroxidase-like DNAzymes) were combined with the consensus sequence recognized by specific transcription factors (either TATA binding protein or the microphthalmia-associated transcription factor).…”

Section: Rational Design Of Allosteric Systems and Identification Of mentioning

confidence: 99%

Allostery in Its Many Disguises: From Theory to Applications

et al. 2019

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Allosteric regulation plays an important role in many biological processes, such as signal transduction, transcriptional regulation, and metabolism. Allostery is rooted in the fundamental physical properties of macromolecular systems, but its underlying mechanisms are still poorly understood. A collection of contributions to a recent interdisciplinary CECAM (Center Européen de Calcul Atomique et Moléculaire) workshop is used hereto provide an overview of the progress and remaining limitations in the understanding of the mechanistic foundations of allostery gained from computational and experimental analyses of real protein systems and model systems. The main conceptual frameworks instrumental in driving the field are discussed. We illustrate the role of these frameworks in illuminating molecular mechanisms and explaining cellular processes, and describe some of their promising practical applications in engineering molecular sensors and informing drug design efforts.

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Section: Rational Design Of Allosteric Systems and Identification Of mentioning

confidence: 99%

Allostery in Its Many Disguises: From Theory to Applications

et al. 2019

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“…Engineering complex self-regulation mechanisms using simple molecular assembly provides a quantitative and programmable chemical strategy to develop and optimize nanosystems with applications ranging from biosensing 49 to chemical computing 50,51 and drug delivery 52,53 . For example, current strategies to extend the dynamic range of sensors consist of combining two or multiple sensors with different affinities [54][55][56] .…”

Section: Discussionmentioning

confidence: 99%

Programming complex regulation mechanisms through simple molecular assembly

Lauzon

Vallée‐Bélisle

2020

Preprint

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What are the advantages and disadvantages of building nanosystems using one or multiple components? More than 55% of all proteins found in living organisms are multimeric and likely exploit molecular assembly to create new functional entities. However, the specific contribution of molecular assembly to the creation of novel functions remains relatively unexplored at the thermodynamic, kinetic and molecular levels. Here, we use theory and a simple experimental model to determine the design rules for engineering efficient self-assembled, self-regulated nanosystems. Using these rules, we have rationally designed and implemented various regulation mechanisms (e.g., cooperative and anticooperative assembly, self-inhibition, molecular timer) into two model trimeric nanosystems including a complex artificial catalyst. These simple strategies based on molecular assembly have been extensively exploited by natural biosystems and are expected to play a crucial role in the development of future self-regulated nanotechnologies.

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“…Controlled Molecule Release : Inspired by the performance of hemoglobin, Mariottini synthesized the first hemoglobin‐like DNA‐based nanodevice with up to four interacting binding sites that realized ligand loading and releasing over narrow concentration ranges, and the ligand affinity could be controlled via both allosteric effectors and by environmental cues (i.e., temperature and pH) . Jeong et al prepared an electro‐responsive multilayer nanofilm on the surface of a chip‐electrode, which enabled controlled release of DNA strand responding to electrochemical inputs . The “sense‐and‐treat” localized the drug delivery system, in which the aptamer accompanied DNA tetrahedron to specifically destroy circulating tumor cells by synergetic chemotherapy with DOX and photodynamic therapy with generating toxic 1 O 2 .…”

Section: Biomedical Applicationsmentioning

confidence: 99%

Programmable and Multifunctional DNA‐Based Materials for Biomedical Applications

et al. 2018

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DNA encodes the genetic information; recently, it has also become a key player in material science. Given the specific Watson-Crick base-pairing interactions between only four types of nucleotides, well-designed DNA self-assembly can be programmable and predictable. Stem-loops, sticky ends, Holliday junctions, DNA tiles, and lattices are typical motifs for forming DNA-based structures. The oligonucleotides experience thermal annealing in a near-neutral buffer containing a divalent cation (usually Mg ) to produce a variety of DNA nanostructures. These structures not only show beautiful landscape, but can also be endowed with multifaceted functionalities. This Review begins with the fundamental characterization and evolutionary trajectory of DNA-based artificial structures, but concentrates on their biomedical applications. The coverage spans from controlled drug delivery to high therapeutic profile and accurate diagnosis. A variety of DNA-based materials, including aptamers, hydrogels, origamis, and tetrahedrons, are widely utilized in different biomedical fields. In addition, to achieve better performance and functionality, material hybridization is widely witnessed, and DNA nanostructure modification is also discussed. Although there are impressive advances and high expectations, the development of DNA-based structures/technologies is still hindered by several commonly recognized challenges, such as nuclease instability, lack of pharmacokinetics data, and relatively high synthesis cost.

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A DNA Nanodevice That Loads and Releases a Cargo with Hemoglobin-Like Allosteric Control and Cooperativity

Cited by 33 publications

References 51 publications

Allostery in Its Many Disguises: From Theory to Applications

Allostery in Its Many Disguises: From Theory to Applications

Programming complex regulation mechanisms through simple molecular assembly

Programmable and Multifunctional DNA‐Based Materials for Biomedical Applications

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