Interaction character between ferulic acid derivatives and bitter taste receptors regulated the bitterness perception via combined assessment of electronic tongue and optimal protein model.

The study of interaction between phenolic compounds and the bitter receptor is rare. Therefore, the current study employed an electronic tongue for investigating the association of the phenolic structure with its corresponding bitterness suppression. Following the preparation of ferulic acid (FA) derivatives, computational simulation techniques are integrated to analyze the interaction mechanisms between ferulic acid and its derivatives with bitter taste receptors at the biomolecular level, thereby establishing a preliminary structure-activity relationship concerning bitterness suppression. The study indicated that the B series derivatives exhibit a superior effect in suppressing bitterness in highly efficient sweetener system, which might be attributed to the enhanced hydrophobicity of the substituents, allowing them to form more robust hydrophobic interactions with bitter taste receptors. In contrast, compounds leucine and caffeine were found to activate a greater number of bitter taste receptors. More importantly, this is the first time to reveal that the absence of appropriately sized hydrophobic spatial structures plus a reduced hydrogen bonding capability led to the inferior bitterness suppression of the B series derivatives compared to FA. Among the C series derivatives, C3 demonstrated a superior bitterness suppression effect, suggesting that the double bond in the acrylic acid structure enhances bitterness suppression. Furthermore, the carbon chain structure may adopt a more favorable conformation for binding to bitter taste receptors, thereby strengthening the bitterness suppression efficacy.