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Disulfide‐Linked Allosteric Modulators for Multi‐cycle Kinetic Control of DNA‐Based Nanodevices
Author(s) -
Del Grosso Erica,
Ponzo Irene,
Ragazzon Giulio,
Prins Leonard J.,
Ricci Francesco
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202008007
Subject(s) - nanodevice , allosteric regulation , dna , ligand (biochemistry) , redox , chemistry , gating , nucleobase , biophysics , combinatorial chemistry , nanotechnology , materials science , enzyme , biochemistry , biology , receptor , organic chemistry
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.