Identification of novel α-glucosidase inhibitory peptides in Meretrix meretrix Linnaeus and their inhibitory kinetics using in silico and in vitro analyses.

This study aimed to identify novel peptides with α-glucosidase inhibitory activity from Meretrix meretrix Linnaeus hydrolysates (MMLHs) following simulated gastrointestinal digestion (SGD) and to elucidate their inhibitory mechanisms. The molecular weight distribution of MMLHs progressively decreased during SGD, with hydrolysates from the intestinal digestion phase (MMLHs-I) exhibiting the strongest α-glucosidase inhibition (IC50: 0.14 ± 0.02 mg/mL). A total of 127 peptides were identified in MMLHs-I, among which 58 were unique compared to those from the gastric digestion phase. In silico screening and molecular docking identified six novel peptides-FAGDDAPR, VPLF, YRRL, WDH, PPLA, and WSG-with significant α-glucosidase inhibitory activity, displaying IC50 values of 0.90, 1.30, 1.90, 1.20, 1.00, and 1.80 mg/mL, respectively. Among them, FAGDDAPR and PPLA exhibited the highest bioactivity. Kinetic analysis and fluorescence quenching assays demonstrated that both peptides acted as mixed-type inhibitors, forming stable complexes with α-glucosidase. Their inhibitory effects were primarily driven by hydrogen bonding and hydrophobic interactions, which hindered substrate binding and induced conformational changes in the enzyme. These findings suggest that peptides derived from MMLHs through gastrointestinal digestion possess potential antidiabetic properties, highlighting their promise as functional food ingredients for mitigating hyperglycemic damage.