Allosteric Nucleic Acid Enzyme: A Versatile Stimuli-Responsive Tool for Molecular Computing and Biosensing Nanodevices.

Allostery is a naturally occurring mechanism in which effector binding induces the modulation and fine control of a related biomolecule function. Deoxyribozyme (DNAzyme) with catalytic activity and substrate recognition ability is ideal to be regulated by allosteric strategies. However, the current regulations frequently confront various obstacles, such as severe activity decay, signal leakage, and limited effectors. In this work, a rational regulation strategy for developing versatile effectors-responsive allosteric nucleic acid enzyme (ANAzyme) by introducing an allosteric domain in response to diverse effectors is established. The enzyme-like activity of this re-engineered ANAzyme can be modulated in a more predictable and fine way compared with the previous DNAzyme regulation strategies. Based on the allosteric strategy, the construction of allosterically coregulatory nanodevices and a series of basic logic gates and logic circuits are achieved, demonstrating that the proposed ANAzyme-regulated strategy showed great potential in molecular computing. Given these facts, the rational design of ANAzyme with the allosteric domain presented here can expand the available toolbox to develop a variety of stimuli-responsive allosteric DNA materials, including molecular machines, computing systems, biosensing platforms, and gene-silencing tools.