Alternation in sequence features and their influence on the anti-inflammatory activity of soy peptides during digestion and absorption in different enzymatic hydrolysis conditions.

This study investigated the anti-inflammatory properties and sequence variations of soy peptides during simulated digestion and absorption. Results showed that 500 Da peptides with N-terminal Leu, Ile, and Tyr exhibited enhanced intestinal transport, while the absorbed peptides in the Bromelain + Flavourzyme group (SIA-BF) demonstrated the strongest anti-inflammatory activity by inhibiting IκB phosphorylation. Mass spectrometry revealed that SIA-BF peptides were rich in branched-chain amino acids at the N-terminus and basic amino acids at the C-terminus. Molecular docking and cellular experiments confirmed that peptides with key terminal amino acids, such as LLVK, exhibited lower binding energies with IκB, stabilizing it and reducing inflammatory cytokines and chemokines. LLVK showed the highest anti-inflammatory efficacy. This study highlights the significance of terminal amino acids in peptide function and provides insights into developing soy peptide-based functional foods for inflammation prevention.