Identification of novel xanthine oxidase inhibitory peptides from Takifugu obscurus: Peptidomic analysis, molecular docking, and dynamics simulation

Hyperuricemia, caused by abnormal purine metabolism, is commonly treated with xanthine oxidase (XOD) inhibitors, uricosuric, and dietary adjustments. Recently, marine-derived bioactive peptides have gained attention as potential functional food ingredients due to their therapeutic potential. Takifugu obscurus, an economically significant offshore fish rich in crude proteins was explored in this study as a source of XOD inhibitory peptides. Enzyme hydrolysis combined with computer simulation identified TOH-A > 1 kDa and TOH-P > 1 kDa hydrolysates with high XOD inhibition rates, which were further selected for peptidomics characterization. After screening, seven peptides were synthesized, four of which (W11, DD7, WY7, and GA9) had inhibitory activity, with W11 showing the lowest IC₅₀. The combination of molecular docking positions with molecular dynamics simulations explains that W11, DD7, and WY7 have the potential to be used to alleviate hyperuricemia. This study provides new insights into the structural mechanism and screening strategy of novel bioactive peptides in the future.