Plasmon-Enhanced Fluorescent Sensor based on Aggregation-Induced Emission for the Study of Protein Conformational Transformation

The alteration in protein conformation not only affects the performance of its biological functions, but also leads to a variety of protein-mediated diseases. Developing a sensitive strategy for protein detection and monitoring its conformation changes is of great significance for the diagnosis and treatment of protein conformation diseases. Herein, a plasmon-enhanced fluorescence (PEF) sensor is developed, based on an aggregation-induced emission (AIE) molecule to monitor conformational changes in protein, using prion protein as a model. Three anthracene derivatives with AIE characteristics are synthesized and a water-miscible sulfonate salt of 9,10-bis(2-(6-sulfonaphthalen-2-yl)vinyl)anthracene (BSNVA) is selected to construct the PEF-AIE sensor. The sensor is nearly non-emissive when it is mixed with cellular prion protein while emits fluorescence when mixed with disease-associated prion protein (PrPSc). The kinetic process of conformational conversion can be monitored through the fluorescence changes of the PEF-AIE sensor. By right of the amplified fluorescence signal, this PEF-AIE sensor can achieve a detection limit 10 pM lower than the traditional AIE probe and exhibit a good performance in human serum sample. Furthermore, molecular docking simulations suggest that BSNVA tends to dock in the beta-sheet structure of PrP by hydrophobic interaction between BSNVA and the exposed hydrophobic residues.