Identification, characterization and molecular docking study of pancreatic lipase inhibitory peptides from bovine...

Bovine blood is a protein-rich by-product of the meat industry, yet its potential as a source of bioactive peptides remains underexplored. Pancreatic lipase (PL) is a key enzyme in lipid digestion, and its inhibition represents a promising strategy for managing obesity. This study aimed to identify and characterize novel PL inhibitory peptides derived from bovine blood and to elucidate their binding mechanisms through molecular docking.

Bovine blood proteins were hydrolyzed using a multi-enzyme system, 592 peptides were identified using liquid chromatography coupled with tandem mass spectrometry. Through virtual screening based on docking energy, toxicity prediction, and PeptideRanker scores, the peptides TQRFF and FTPVF were prioritized for analysis. Subsequently, molecular docking analysis revealed that TQRFF stabilized the PL complex through hydrogen bonding as well as cation-π, π-π, π-alkyl and alkyl interactions. Meanwhile, FTPVF formed salt bridges and demonstrated hydrogen bonding, cation-π interactions, π-π interactions and alkyl interactions. Molecular dynamics simulations revealed greater conformational stability in the FTPVF-PL complex, whereas TQRFF was found to induce protein compaction and form stronger hydrogen bonds. Finally, in in vitro experiments conducted after synthesizing these two key peptides, both TQRFF and FTPVF exhibited potent in vitro PL inhibitory activity, with half maximal inhibitory concentration (IC₅₀) values of 260.02 ± 17.01 μg mL^-1 and 760.04 ± 59.03 μg mL^-1, respectively.

The bovine blood-derived peptides TQRFF and FTPVF are novel PL inhibitors with promising anti-obesity potential. Their binding modes involve key interactions with the active site residues, supporting further development as functional food ingredients. © 2026 Society of Chemical Industry.