Discovery of N-L-Lactoyl-L-Trp as a Bitterness Masker via Structure-Based Virtual Screening and a Sensory Approach

N-Lactoyl-amino acid derivatives (N-Lac-AAs) are of increasing interest as potential taste-active compounds. The complexity and diversity of N-Lac-AAs pose a significant challenge to the effective discovery of taste-active N-Lac-AAs. Therefore, a structure-based virtual screening was used to identify taste-active N-Lac-AAs. Virtual screening results showed that N-lactoyl-hydrophobic amino acids had a higher affinity for taste receptors, specifically N-L-Lac-L-Trp. And then, N-L-Lac-L-Trp was synthesized in yields of 22.3% by enzymatic synthesis in the presence of L-lactate and L-Trp, and its chemical structure was confirmed by MS/MS and one-dimensional (1D) and two-dimensional (2D) NMR. Sensory evaluation revealed that N-L-Lac-L-Trp had a significant taste-masking effect on quinine, D-salicin, caffeine, and L-Trp, particularly L-Trp and caffeine. N-L-Lac-L-Trp had a better masking effect on the higher concentration of bitter compounds. It reduced the bitterness of caffeine (500 mg/L) and L-Trp (1000 mg/L) by approximately 20 and 26%, respectively. The result of the ligand-receptor interaction and a quantum mechanical analysis showed that N-L-Lac-L-Trp increased the binding affinity to the bitter receptor mainly through hydrogen bonding and lowering the electrostatic potential.

Automated summary

A structure-based virtual screening was used to identify taste-active N-Lac-AAs, with N-L-Lac-L-Trp showing higher affinity for taste receptors. N-L-Lac-L-Trp was synthesized and its chemical structure was confirmed. Sensory evaluation revealed that N-L-Lac-L-Trp had a significant taste-masking effect on quinine, D-salicin, caffeine, and L-Trp, particularly L-Trp and caffeine.