Identification and Molecular Binding Mechanism of Novel α-Glucosidase Inhibitory Peptides from Hot-Pressed Peanut Meal Protein Hydrolysates

Hot-pressed peanut meal protein hydrolysates are rich in Arg residue, but there is a lack of research on their alpha-glucosidase inhibitory activity. In this study, different proteases were used to pro-duce hot-pressed peanut meal protein hydrolysates (PMHs) to evaluate the alpha-glucosidase inhibitory activity. All PMHs showed good alpha-glucosidase inhibitory activity with the best inhibition effect coming from the dual enzyme system of Alcalase and Neutrase with an IC50 of 5.63 +/- 0.19 mg/mL. The fractions with the highest inhibition effect were separated and purified using ultrafiltration and cation exchange chromatography. Four novel alpha-glucosidase inhibitory peptides (FYNPAAGR, PGVLPVAS, FFVPPSQQ, and FSYNPQAG) were identified by nano-HPLC-MS/MS and molecular docking. Molecular docking showed that peptides could occupy the active pocket of alpha-glucosidase through hydrogen bonding, hydrophobic interaction, salt bridges, and n-stacking, thus preventing the formation of complexes between alpha-glucosidase and the substrate. In addition, the alpha-glucosidase inhibitory activity of PMHs was stable against hot, pH treatment and in vitro gastrointestinal digestion. The study demonstrated that PMHs might be used as a natural anti-diabetic material with the potential to inhibit alpha-glucosidase.

Automated summary

Hot-pressed peanut meal protein hydrolysates (PMHs) were produced using different proteases to evaluate their alpha-glucosidase inhibitory activity. All PMHs showed good inhibition, but the dual enzyme system of Alcalase and Neutrase had the best effect with an IC50 of 5.63 +/- 0.19 mg/mL. Four novel inhibitory peptides were identified through nano-HPLC-MS/MS and molecular docking. These peptides could occupy the active pocket of alpha-glucosidase, preventing the formation of complexes. Additionally, the inhibitory activity of PMHs was stable against various treatments. PMHs could be used as a natural anti-diabetic material.