Allosteric Control of Oxidative Catalysis by a DNA Rotaxane Nanostructure.

DNA is a versatile construction material for the bottom-up assembly of structures and functional devices in the nanoscale. Additionally, there are specific sequences called DNAzymes that can fold into tertiary structures that display catalytic activity. Here we report the design of an interlocked DNA nanostructure that is able to fine-tune the oxidative catalytic activity of a split DNAzyme in a highly controllable manner. As scaffold, we employed a double-stranded DNA rotaxane for its ability to undergo programmable and predictable conformational changes. Precise regulation of the DNAzyme's oxidative catalysis can be achieved by external stimuli (i.e., addition of release oligos) that modify the spatial arrangement within the system, without interfering with the catalytic core, similar to structural rearrangements that occur in allosterically controlled enzymes. We show that multiple switching steps between the active and inactive conformations can be performed consistent with efficient regulation and robust control of the DNA nanostructure.

[1]  Michael Famulok,et al.  Pseudo-complementary PNA actuators as reversible switches in dynamic DNA nanotechnology , 2013, Nucleic acids research.

[2]  Xi Chen,et al.  Rational, modular adaptation of enzyme-free DNA circuits to multiple detection methods , 2011, Nucleic acids research.

[3]  Michael Famulok,et al.  Interlocked DNA nanostructures controlled by a reversible logic circuit , 2014, Nature Communications.

[4]  H. Dietz,et al.  Placing molecules with Bohr radius resolution using DNA origami. , 2016, Nature nanotechnology.

[5]  Itamar Willner,et al.  Au nanoparticle/DNA rotaxane hybrid nanostructures exhibiting switchable fluorescence properties. , 2013, Nano letters.

[6]  I. Willner,et al.  Switchable Reconfiguration of a Seven-Ring Interlocked DNA Catenane Nanostructure. , 2015, Nano letters.

[7]  Hao Yan,et al.  Structural DNA Nanotechnology: State of the Art and Future Perspective , 2014, Journal of the American Chemical Society.

[8]  Xiang Zhou,et al.  Highly effective colorimetric and visual detection of nucleic acids using an asymmetrically split peroxidase DNAzyme. , 2008, Journal of the American Chemical Society.

[9]  Itamar Willner,et al.  Programmed dynamic topologies in DNA catenanes. , 2012, Angewandte Chemie.

[10]  F. Ricci,et al.  A general approach to the design of allosteric, transcription factor-regulated DNAzymes , 2015, Chemical science.

[11]  Zhao Zhang,et al.  DNA Origami Rotaxanes: Tailored Synthesis and Controlled Structure Switching. , 2016, Angewandte Chemie.

[12]  Itamar Willner,et al.  Lighting Up Biochemiluminescence by the Surface Self‐Assembly of DNA–Hemin Complexes , 2004, Chembiochem : a European journal of chemical biology.

[13]  Friedrich C Simmel,et al.  Long-range movement of large mechanically interlocked DNA nanostructures , 2016, Nature Communications.

[14]  Itamar Willner,et al.  Powering the programmed nanostructure and function of gold nanoparticles with catenated DNA machines , 2013, Nature Communications.

[15]  Anna J Simon,et al.  Activity modulation and allosteric control of a scaffolded DNAzyme using a dynamic DNA nanostructure† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c5sc03705k , 2015, Chemical science.

[16]  Julián Valero,et al.  Logic gating by macrocycle displacement using a double-stranded DNA [3]rotaxane shuttle. , 2014, Angewandte Chemie.

[17]  Andrew D. Ellington,et al.  Beyond allostery: Catalytic regulation of a deoxyribozyme through an entropy-driven DNA amplifier , 2010 .

[18]  Giuseppe Palleschi,et al.  Allosteric DNA nanoswitches for controlled release of a molecular cargo triggered by biological inputs† †Electronic supplementary information (ESI) available: Supporting information. See DOI: 10.1039/c6sc03404g Click here for additional data file. , 2016, Chemical science.

[19]  Thomas Tørring,et al.  DNA origami: a quantum leap for self-assembly of complex structures. , 2011, Chemical Society reviews.

[20]  Zhenyu Lin,et al.  Pb(2+)-introduced activation of horseradish peroxidase (HRP)-mimicking DNAzyme. , 2011, Chemical communications.

[21]  Michael Famulok,et al.  Daisy Chain Rotaxanes Made from Interlocked DNA Nanostructures , 2016, Angewandte Chemie.

[22]  Itamar Willner,et al.  Amplified biosensing using the horseradish peroxidase-mimicking DNAzyme as an electrocatalyst. , 2010, Analytical chemistry.

[23]  Thomas A. Singleton,et al.  Switching between Anion-Binding Catalysis and Aminocatalysis with a Rotaxane Dual-Function Catalyst. , 2017, Journal of the American Chemical Society.

[24]  I. Willner,et al.  Switchable reconfiguration of an interlocked DNA olympiadane nanostructure. , 2014, Angewandte Chemie.

[25]  Juwen Shen,et al.  Dynamic Modulation of DNA Hybridization Using Allosteric DNA Tetrahedral Nanostructures. , 2016, Analytical chemistry.

[26]  Itamar Willner,et al.  Aptamer-DNAzyme hairpins for amplified biosensing. , 2009, Analytical chemistry.

[27]  P. Rothemund.  Folding DNA to create nanoscale shapes and patterns , 2006, Nature.

[28]  Michael Famulok,et al.  Design strategy for DNA rotaxanes with a mechanically reinforced PX100 axle. , 2012, Angewandte Chemie.

[29]  Michael Famulok,et al.  A double-stranded DNA rotaxane. , 2010, Nature nanotechnology.

[30]  Michael Famulok,et al.  Reversible Light Switch for Macrocycle Mobility in a DNA Rotaxane , 2012, Journal of the American Chemical Society.

[31]  N. Seeman.  DNA in a material world , 2003, Nature.

[32]  Hao Yan,et al.  Dna Origami: a History and Current Perspective This Review Comes from a Themed Issue on Nanotechnology and Miniaturization Edited Structural Development Assembly Approaches Single-molecule Detection Material Organization , 2022 .