Rational Construction of Protein-Mimetic Nano-Switch Systems Based on Secondary Structure Transitions of Synthetic Polypeptides

The manipulation of the flexibility/rigidityof polymeric chainsto control their function is commonly observed in natural macromoleculesbut largely unexplored in synthetic systems. Herein, we constructa series of protein-mimetic nano-switches consisting of a gold nanoparticle(GNP) core, a synthetic polypeptide linker, and an optically functionalmolecule (OFM), whose biological function can be dynamically regulatedby the flexibility of the polypeptide linker. At the dormant state,the polypeptide adopts a flexible, random-coiled conformation, bringingGNP and OFM in close proximity that leads to the turn-offof the OFM. Once treated with alkaline phosphatase (ALP), the nano-switchesare activated due to the increased separation distance between GNPand OFM driven by the coil-to-helix and flexible-to-rigid transitionof the polypeptide linker. The nano-switches therefore enable selectivefluorescence imaging or photodynamic therapy in response to ALP overproducedby tumor cells. The control over polymer flexibility represents aneffective strategy to manipulate the optical activity of nano-switches,which mimics the delicate structure-property relationship ofnatural proteins.

Automated summary

In this study, a series of protein-mimetic nano-switches were constructed to control their function based on the flexibility/rigidity of the polymeric chains. When in a dormant state, the polypeptide adopts a flexible, random-coiled conformation, leading to the turn-off of the optically functional molecule. Upon treatment with alkaline phosphatase, the nano-switches are activated due to the coil-to-helix and flexible-to-rigid transition of the polypeptide linker, enabling selective fluorescence imaging or photodynamic therapy in response to ALP overproduced by tumor cells.