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A general approach to the design of allosteric, transcription factor-regulated DNAzymes

Here we explore a general strategy for the rational design of nucleic acid catalysts that can be allosterically activated by specific nucleic-acid binding proteins. To demonstrate this we have combined a catalytic DNAzyme sequence and the consensus sequence recognized by specific transcription facto...

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Autores principales: Adornetto, G., Porchetta, A., Palleschi, G., Plaxco, K. W., Ricci, F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Royal Society of Chemistry 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496187/
https://www.ncbi.nlm.nih.gov/pubmed/28706715
http://dx.doi.org/10.1039/c5sc00228a
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author Adornetto, G.
Porchetta, A.
Palleschi, G.
Plaxco, K. W.
Ricci, F.
author_facet Adornetto, G.
Porchetta, A.
Palleschi, G.
Plaxco, K. W.
Ricci, F.
author_sort Adornetto, G.
collection PubMed
description Here we explore a general strategy for the rational design of nucleic acid catalysts that can be allosterically activated by specific nucleic-acid binding proteins. To demonstrate this we have combined a catalytic DNAzyme sequence and the consensus sequence recognized by specific transcription factors to create a construct exhibiting two low-energy conformations: a more stable conformation lacking catalytic activity and lacking the transcription factor binding site, and a less stable conformation that is both catalytically active and competent to bind the transcription factor. The presence of the target transcription factor pushes the equilibrium between these states towards the latter conformation, concomitantly activating catalysis. To demonstrate this we have designed and characterized two peroxidase-like DNAzymes whose activities are triggered upon binding either TATA binding protein or the microphthalmia-associated transcription factor. Our approach augments the current tool kit for the allosteric control of DNAzymes and ribozymes and, because transcription factors control many key biological functions, could have important clinical and diagnostic applications.
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spelling pubmed-54961872017-07-13 A general approach to the design of allosteric, transcription factor-regulated DNAzymes Adornetto, G. Porchetta, A. Palleschi, G. Plaxco, K. W. Ricci, F. Chem Sci Chemistry Here we explore a general strategy for the rational design of nucleic acid catalysts that can be allosterically activated by specific nucleic-acid binding proteins. To demonstrate this we have combined a catalytic DNAzyme sequence and the consensus sequence recognized by specific transcription factors to create a construct exhibiting two low-energy conformations: a more stable conformation lacking catalytic activity and lacking the transcription factor binding site, and a less stable conformation that is both catalytically active and competent to bind the transcription factor. The presence of the target transcription factor pushes the equilibrium between these states towards the latter conformation, concomitantly activating catalysis. To demonstrate this we have designed and characterized two peroxidase-like DNAzymes whose activities are triggered upon binding either TATA binding protein or the microphthalmia-associated transcription factor. Our approach augments the current tool kit for the allosteric control of DNAzymes and ribozymes and, because transcription factors control many key biological functions, could have important clinical and diagnostic applications. Royal Society of Chemistry 2015-07-01 2015-03-10 /pmc/articles/PMC5496187/ /pubmed/28706715 http://dx.doi.org/10.1039/c5sc00228a Text en This journal is © The Royal Society of Chemistry 2015 http://creativecommons.org/licenses/by/3.0/ This article is freely available. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence (CC BY 3.0)
spellingShingle Chemistry
Adornetto, G.
Porchetta, A.
Palleschi, G.
Plaxco, K. W.
Ricci, F.
A general approach to the design of allosteric, transcription factor-regulated DNAzymes
title A general approach to the design of allosteric, transcription factor-regulated DNAzymes
title_full A general approach to the design of allosteric, transcription factor-regulated DNAzymes
title_fullStr A general approach to the design of allosteric, transcription factor-regulated DNAzymes
title_full_unstemmed A general approach to the design of allosteric, transcription factor-regulated DNAzymes
title_short A general approach to the design of allosteric, transcription factor-regulated DNAzymes
title_sort general approach to the design of allosteric, transcription factor-regulated dnazymes
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496187/
https://www.ncbi.nlm.nih.gov/pubmed/28706715
http://dx.doi.org/10.1039/c5sc00228a
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