Simulated gastrointestinal digestion of the corn gluten meal peptide DV-12 to DA-11 substantially reduced its ACE-inhibitory potency, increasing Ki from 8 μM to 1.06 mM.
Subtle structural modifications during digestion can markedly alter the bioactivity of ACE-inhibitory peptides derived from food sources, highlighting the need to consider downstream functional fate in functional food development.
Corn gluten meal (CGM) is an underutilized byproduct with rigid structure, which limits efficient peptide release during enzymatic hydrolysis. While microwave pretreatment can disrupt the rigid CGM matrix and enhance peptide release, this study investigated how downstream gastrointestinal modification and transport behavior ultimately influence the functional fate of the enzymatically liberated peptide sequences. Enzymatic hydrolysis of microwave-pretreated CGM led to a 3.3-fold increase in peptide yield while maintaining angiotensin-converting enzyme (ACE)-inhibitory activity at a level comparable to that of the untreated CGM hydrolysate. From this digest, the purified peptide DVPSADAPAAAV (DV-12) exhibited potent in vitro ACE inhibition (IC₅₀ = 57.25 μM). Simulated gastrointestinal digestion partially hydrolyzed DV-12 to DVPSADAPAAA (DA-11), a minor structural modification that was overestimated by in silico digestion models yet resulted in a substantial reduction in ACE-inhibitory potency. Kinetic analysis and molecular dynamics simulations revealed that this truncation fundamentally altered peptide–ACE interactions: DV-12 ( K ᵢ = 8 μM) maintained more stable coordination near the ACE Zn 2+ catalytic center, whereas DA-11 displayed substantially weaker binding ( K ᵢ = 1.06 mM). In Caco-2 monolayers, both peptides crossed the epithelial barrier at low rates, with apparent permeability coefficients of 9.96 × 10 −8 and 8.23 × 10 −8 cm·s −1 for DV-12 and DA-11, respectively, while unabsorbed peptide fractions, particularly DV-12, concurrently reduced intracellular reactive oxygen species. These findings demonstrated that increasing peptide yield alone does not guarantee preserved downstream functionality, as subtle structural modifications occurring during digestion and transport toward absorption could markedly alter peptide bioactivity and should therefore be considered in the development of functional food ingredients.
Hamzeh et al. (Wed,) reported a other. Microwave-pretreated corn gluten meal peptides vs. Untreated corn gluten meal hydrolysate was evaluated on ACE-inhibitory activity. Simulated gastrointestinal digestion of the corn gluten meal peptide DV-12 to DA-11 substantially reduced its ACE-inhibitory potency, increasing Ki from 8 μM to 1.06 mM.