AIE-Active Probe for Unveiling the Role of Protein Sulfenylation In Vivo: Specific Imaging and Therapeutic Insights.

Abstract

Protein sulfenylation (protein-SOH) is a central oxidation product of protein post-translational modification (PTM) that is crucial for signal transduction and cell behavior. However, the natural properties of protein-SOH, especially its low responsiveness and dynamic reversibility, pose a great challenge to the development of chemical probes to visualize protein-SOH in vivo. Here, we report an activated aggregation-induced emission (AIE) probe for specifically lighting-up protein-SOH in vivo. The AIE-active probe reacts with protein-SOH by nucleophilic substitution and exhibits intense fluorescence due to the restriction of intramolecular motion. The uniqueness of this probe ensures that fluorescence is only lighted up by protein-SOH, avoiding interference from small-molecule active substances and nonspecific adsorption of proteins. The significant increase of protein-SOH in atherosclerotic mice is detected by the AIE probe, and the level of protein-SOH positively correlates with atherosclerosis progression. Significantly, we find that specific binding of protein-SOH by this probe can inhibit plaque development, making it a promising therapeutic target. This study enables real-time imaging of protein oxidation modification in vivo, opening up a universal chemical tool for further elucidation of PTM and its role in signal transduction.