Movable toehold for leakless self-assembly circuits

Abstract

Nonenzymatic self-assembly circuit utilizing hairpin substrates has been developed to be a powerful tool for information transduction, amplification and computation. However, the sensitivity, stability and application of this circuit are impeded by the presence of leakage which refers to undesired triggering in the absence of input. Herein, we proposed a movable toehold principle to suppress leakage and accelerate the catalytic reaction through removing partial hairpin toehold responsible for the leakage and transferring it to the catalyst. With movable toehold, catalytic hairpin assembly (called mtCHA) exhibited an excellent signal-to-background ratio of over 100, high robustness and improved specificity. In more complex circuit, including proximity recognition, signal amplification of small molecules (such as ATP), logic network, autocatalysis circuit and two-layer cascade circuit, mtCHA also demonstrated satisfactory performance. Our findings suggest that mtCHA holds great potential for broader applications, and the approach of repurposing harmful fragments into beneficial candidates can provide valuable insights for other chemical systems.