Disulfide‐Linked Allosteric Modulators for Multi‐cycle Kinetic Control of DNA‐Based Nanodevices

Abstract

Nature employs sulfur switches, that is, redox‐active disulfides, to kinetically control biological pathways in a highly efficient and reversible way. Inspired by this mechanism, we describe herein a DNA‐based synthetic nanodevice that acts as a sulfur switch and can be temporally controlled though redox regulation. To do this, we rationally designed disulfide DNA strands (modulators) that hybridize to a ligand‐binding DNA nanodevice and act as redox‐active allosteric regulators inducing the nanodevice to release or load its ligand. Upon reduction, the allosteric modulator spontaneously de‐hybridizes from the nanodevice and, as a result, its effect is transient. The system is reversible and has an unprecedented high tolerance to waste products and displays transient behavior for over 40 cycles without significant loss of efficiency. Kinetic control of DNA‐based ligand‐binding nanodevices through purely chemical reactions paves the way for temporal regulation of more complex chemical pathways.

Dissipative Control over the Toehold‐Mediated DNA Strand Displacement Reaction

“…Within the context of creating artificial dissipative nanodevices [17–22] and structures, [23–26] synthetic DNA has been rapidly emerging as a powerful material. The programmability and predictability of DNA hybridization, together with the possibility to use nucleic acids as fuels that can be enzymatically or chemically fragmented into waste, have been providing a strong momentum for the establishment of the field of dissipative DNA nanotechnology [17–26] .…”

“…Within the context of creating artificial dissipative nanodevices [17–22] and structures, [23–26] synthetic DNA has been rapidly emerging as a powerful material. The programmability and predictability of DNA hybridization, together with the possibility to use nucleic acids as fuels that can be enzymatically or chemically fragmented into waste, have been providing a strong momentum for the establishment of the field of dissipative DNA nanotechnology [17–26] . Contrary to classical dynamic DNA nanotechnology, [27] which relies on the chemically‐triggered activation of complex kinetic pathways that transit into new thermodynamic final states, dissipative DNA technology is based on reactions which enable a transient and repetitive activation of the system through the batch‐wise addition of fuel (Figure 1).…”

Reorganization of Self‐Assembled DNA‐Based Polymers using Orthogonally Addressable Building Blocks**

“…Synthetic nucleic acid strands (DNAa nd RNA) have emerged as ideal components for self-assembly processes.The high programmability and the possibility to predict in as traightforward way the thermodynamics of the involved non-covalent hydrogen bond base pairings,together with the low cost of synthesis,h as allowed the self-assembly of unprecedented precise 2D and 3D structures,h ydrogels, nanodevices and polymers from rationally designed synthetic DNAo ligonucleotides. [39][40][41][42][43][44][45] Recently,t he possibility to reconfigure these structures has also been demonstrated enabling dynamic DNAs tructures with potential adaptive behavior. [46][47][48][49][50][51] Motivated by the above arguments and taking advantage of the addressability of DNAw es how here that synthetic nucleic acids are particularly suited for designing self-assembling dynamic polymer-like structures that can be easily reconfigured and reorganized by external inputs.T od ot his we have rationally designed monomer units that can be orthogonally addressed by different DNAr egulator strands and can be used to structurally reorganize the polymers between homopolymers,r andom co-polymers and two-tile and three-tile block co-polymers (Figure 1d).…”

“…Synthetic nucleic acid strands (DNA and RNA) have emerged as ideal components for self‐assembly processes. The high programmability and the possibility to predict in a straightforward way the thermodynamics of the involved non‐covalent hydrogen bond base pairings, together with the low cost of synthesis, has allowed the self‐assembly of unprecedented precise 2D and 3D structures, hydrogels, nanodevices and polymers from rationally designed synthetic DNA oligonucleotides [39–45] . Recently, the possibility to reconfigure these structures has also been demonstrated enabling dynamic DNA structures with potential adaptive behavior [46–51] …”

Reorganization of Self-Assembled DNA-Based Polymers Using Orthogonally Addressable Building Blocks

“…The high programmability and the possibility to predict in a straightforward way the thermodynamics of the involved non-covalent hydrogen bond base pairings, together with the low cost of synthesis, has allowed the self-assembly of unprecedented precise 2D and 3D structures, hydrogels, nanodevices and polymers from rationally designed synthetic DNA oligonucleotides. [39][40][41][42][43][44][45] Recently, the possibility to reconfigure these structures has also been demonstrated enabling dynamic DNA structures with potential adaptive behaviour. [46][47][48][49][50][51] Motivated by the above arguments and taking advantage of the addressability of DNA we show here that synthetic nucleic acids are particularly suited for designing selfassembling dynamic polymer-like structures that can be easily reconfigured and reorganized by external inputs.…”