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Heterochiral DNA Strand-Displacement Based on Chimeric d/l-Oligonucleotides

Cite this: ACS Synth. Biol. 2019, 8, 12, 2756–2759
Publication Date (Web):October 31, 2019
https://doi.org/10.1021/acssynbio.9b00335
Copyright © 2019 American Chemical Society

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    Abstract

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    Heterochiral DNA strand-displacement reactions enable sequence-specific interfacing of oligonucleotide enantiomers, making it possible to interface native d-nucleic acids with molecular circuits built using nuclease-resistant l-DNA. To date, all heterochiral reactions have relied on peptide nucleic acid (PNA), which places potential limits on the scope and utility of this approach. Herein, we now report heterochiral strand-displacement in the absence of PNA, instead utilizing chimeric d/l-DNA complexes to interface oligonucleotides of the opposite chirality. We show that these strand-displacement reactions can be easily integrated into multicomponent heterochiral circuits, are compatible with both DNA and RNA inputs, and can be engineered to function in serum-supplemented medium. We anticipate that these new reactions will lead to a wider application of heterochiral strand-displacement, especially in the design of biocompatible nucleic acid circuits that can reliably operate within living systems.

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acssynbio.9b00335.

    • Materials and Methods; Figures S1–S6; Table S1 (PDF)

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    Cited By

    This article is cited by 7 publications.

    1. Tracy L. Mallette, Matthew R. Lakin. Protecting Heterochiral DNA Nanostructures against Exonuclease-Mediated Degradation. ACS Synthetic Biology 2022, 11 (7) , 2222-2228. https://doi.org/10.1021/acssynbio.2c00105
    2. Tracy L. Mallette, Milan N. Stojanovic, Darko Stefanovic, Matthew R. Lakin. Robust Heterochiral Strand Displacement Using Leakless Translators. ACS Synthetic Biology 2020, 9 (7) , 1907-1910. https://doi.org/10.1021/acssynbio.0c00131
    3. Chaturong Suparpprom, Tirayut Vilaivan. Perspectives on conformationally constrained peptide nucleic acid (PNA): insights into the structural design, properties and applications. RSC Chemical Biology 2022, 3 (6) , 648-697. https://doi.org/10.1039/D2CB00017B
    4. Adam M. Kabza, Nandini Kundu, Wenrui Zhong, Jonathan T. Sczepanski. Integration of chemically modified nucleotides with DNA strand displacement reactions for applications in living systems. WIREs Nanomedicine and Nanobiotechnology 2022, 14 (2) https://doi.org/10.1002/wnan.1743
    5. Erika Schaudy, Mark M. Somoza, Jory Lietard. l ‐DNA Duplex Formation as a Bioorthogonal Information Channel in Nucleic Acid‐Based Surface Patterning. Chemistry – A European Journal 2020, 26 (63) , 14310-14314. https://doi.org/10.1002/chem.202001871
    6. Steven Ochoa, Valeria T. Milam. Modified Nucleic Acids: Expanding the Capabilities of Functional Oligonucleotides. Molecules 2020, 25 (20) , 4659. https://doi.org/10.3390/molecules25204659
    7. Adam M. Kabza, Jonathan T. Sczepanski. l-DNA-Based Catalytic Hairpin Assembly Circuit. Molecules 2020, 25 (4) , 947. https://doi.org/10.3390/molecules25040947

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