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Allosterically Tunable, DNA-Based Switches Triggered by Heavy Metals

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    Allosterically Tunable, DNA-Based Switches Triggered by Heavy Metals
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    † Dipartimento di Scienze e Tecnologie Chimiche, University of Rome, Tor Vergata, Via della Ricerca Scientifica, 00133, Rome, Italy
    ‡ Consorzio Interuniversitario Biostrutture e Biosistemi “INBB”, Rome, Italy
    § Laboratory of Biosensors and Nanomachines, Département de Chimie, Université de Montréal, Montreal, Québec, Canada
    ∥ ⊥ ∥Center for Bioengineering & Department of Chemistry and Biochemistry; ⊥Interdepartmental Program in Biomolecular Science and Engineering, University of California, Santa Barbara, California 93106, United States
    [email protected]
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    Cite this: J. Am. Chem. Soc. 2013, 135, 36, 13238–13241
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    https://doi.org/10.1021/ja404653q
    Published August 23, 2013
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    Abstract

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    Here we demonstrate the rational design of allosterically controllable, metal-ion-triggered molecular switches. Specifically, we designed DNA sequences that adopt two low energy conformations, one of which does not bind to the target ion and the other of which contains mismatch sites serving as specific recognition elements for mercury(II) or silver(I) ions. Both switches contain multiple metal binding sites and thus exhibit homotropic allosteric (cooperative) responses. As heterotropic allosteric effectors we employ single-stranded DNA sequences that either stabilize or destabilize the nonbinding state, enabling dynamic range tuning over several orders of magnitude. The ability to rationally introduce these effects into target-responsive switches could be of value in improving the functionality of DNA-based nanomachines.

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    Cite this: J. Am. Chem. Soc. 2013, 135, 36, 13238–13241
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