Combining a protein-targeting small molecule and a thiol-targeting small molecule for detecting a serum risk marker of liver tumor recurrence.

This work proposes a novel bioassay designed to detect the 2B receptor of serotonin in serum samples, which can serve as a risk marker for cancer recurrence after surgical resection. Traditional methods for detecting this marker are often costly and time-consuming, requiring specialized reagents and equipment. The new bioassay is designed to enable direct and reagent-less detection of the 2B receptor in serum samples, without the need of antibodies or enzymes. The assay uses a small molecule ligand for the 2B receptor combined with a thiol-targeting fluorescent dye on a compact peptide-based molecular frame. This design allows for a rapid and specific readout of the fluorescent signal upon probe-protein interaction. In addition, the covalent biosensing process used in the assay allows for signal enhancement by electrochemical cross-linking of serum proteins. The bioassay was successfully used to detect the 2B receptor in serum samples from hepatocarcinoma patients, indicating its potential as a powerful tool for early cancer detection and monitoring.