Peptidomics-guided 3D structural-mechanistic investigation of bovine colostrum peptides reveals multi-targeted in silico and in vitro antidiabetic and antioxidant potential

Abstract

Multi-target inhibition of α-amylase, α-glucosidase, and human aldose reductase can significantly address postprandial hyperglycemia and subsequent diabetic complications, yet bovine colostrum peptides remain largely unscreened against these enzymes. Using a peptidomics-guided, integrated in silico and in vitro approach, we identified three lead peptides and highlighted Peptide P2 (GPAGPQGPR) as a common lead inhibitor, showing favorable predicted binding and interaction profiles relative to the reference inhibitors. A dedicated 3D-structural analysis, including residue mapping, RMSF profiles, hydrophobicity surfaces, and intramolecular contact networks, suggested that the glycine-proline-rich scaffold of P2 may support predicted conformational adaptability and interactions with multiple enzyme targets. These findings were supported by in vitro enzyme inhibition and kinetic analyses, which indicated that P2 was consistent with a competitive inhibition model, while radical scavenging analysis indicated its antioxidant potential. These findings establish bovine colostrum as a potential multi-target antidiabetic and antioxidant peptide source, and present a structure-informed, reproducible framework for food-derived peptide discovery.