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Adornetto G, Porchetta A, Palleschi G, et al. A general approach to the design of allosteric, transcription factor-regulated DNAzymes. Chem Sci. 2015;6(7):3692-3696doi: 10.1039/c5sc00228a.
Adornetto, G., Porchetta, A., Palleschi, G., Plaxco, K. W., & Ricci, F. (2015). A general approach to the design of allosteric, transcription factor-regulated DNAzymes. Chemical science, 6(7), 3692-3696. https://doi.org/10.1039/c5sc00228a
Adornetto, G, et al. "A general approach to the design of allosteric, transcription factor-regulated DNAzymes." Chemical science vol. 6,7 (2015): 3692-3696. doi: https://doi.org/10.1039/c5sc00228a
Adornetto G, Porchetta A, Palleschi G, Plaxco KW, Ricci F. A general approach to the design of allosteric, transcription factor-regulated DNAzymes. Chem Sci. 2015 Jul 15;6(7):3692-3696. doi: 10.1039/c5sc00228a. Epub 2015 Mar 10. PMID: 28706715; PMCID: PMC5496187.
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Chem Sci. 2015 Jul 15;6(7):3692-3696. doi: 10.1039/c5sc00228a. Epub 2015 Mar 10.

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

Chemical science

G Adornetto, A Porchetta, G Palleschi, K W Plaxco, F Ricci

Affiliations

  1. Dipartimento di Scienze e Tecnologie Chimiche University of Rome Tor Vergata , Via della Ricerca Scientifica , Rome 00133 , Italy . Email: [email protected].
  2. Consorzio Interuniversitario Biostrutture e Biosistemi "INBB" , Rome 00136 , Italy.
  3. Department of Chemistry and Biochemistry , University of California Santa Barbara , Santa Barbara , California 93106 , USA.
  4. Center for Bioengineering , University of California Santa Barbara , Santa Barbara , California 93106 , USA.

PMID: 28706715 PMCID: PMC5496187 DOI: 10.1039/c5sc00228a

Abstract

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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