Dynamic Control of Peptide Strand Displacement Reaction using Functional Biomolecular Domain for Biosensing.

Nature's great repository provides nucleic acid and amino acid as the fundamental elements of life. Inspired by the program-mability of nucleic acid, DNA nanotechnology has been exten-sively developed based on the strand displacement reaction of nucleic acid. Comparing with nucleic acid, amino acid possess-es higher programmability and more functionalities owing to the diversity of amino acid unit. However, the design of peptide based bimolecular cascade is still limited. We herein describe a peptide based strand displacement reaction cascade, which was granted a specific biological function by addition of a functional domain onto the coiled-coil peptide based displacement sub-strate. The displacement substrate was specifically designed to response to Tau protein based on a well-established Tau inhibi-tion sequence. We demonstrated that the kinetic of the de-signed displacement reaction can be dynamically tuned through blocking the toehold region to prevent migration. A nano-molar Tau detection linear range was achieved through the designed displacement reaction within a rapid turnaround time of 30 min. We also presented the capability of the peptide strand displacement based sensing system operating in real human biological sample and its excellent orthogonality on response to irrelevant biological components. We envision that this will be of especially high utility for development of next-generation of biotechnology.