Disulfide‐Linked Allosteric Modulators for Multi‐cycle Kinetic Control of DNA‐Based Nanodevices. (8th September 2020)

• Record Type: Journal Article
• Authors: Del Grosso, Erica; Ponzo, Irene; Ragazzon, Giulio; Prins, Leonard J.; Ricci, Francesco
• Is Part Of: Angewandte Chemie. Volume 132:Number 47(2020)
• Page Start: 21244
• Page End: 21249
• Publication Date: 2020-09-08
• Subjects: DNA devices -- DNA nanotechnology -- redox cycles -- supramolecular chemistry -- temporal control; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202008007
• Languages: English
• ISSNs: 0044-8249

Abstract

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. Abstract : We describe a DNA‐based nanodevice that acts as a sulfur switch and can be temporally controlled through redox cycles of a disulfide‐linked allosteric modulator. The system has an unprecedented high tolerance to waste products and displays transient behavior for over 40 cycles without significant loss of efficiency. The approach is reversible and allows the transient loading and release of a ligand upon successive reduction and oxidation of the modulator.