Identification of DPP‐IV inhibitory peptides derived from buffalo colostrum: Mining through bioinformatics, in silico and in vitro approaches

Abstract

Bioactive peptides derived from foods provide physiological health benefits beyond nutrition. This study focused on profiling small peptide inhibitors against two key serine proteases, dipeptidyl peptidase‐IV (DPP‐IV) and prolyl oligopeptidase (POP). DPP‐IV is a well‐known protein involved in diverse pathways regulating inflammation, renal, cardiovascular physiology, and glucose homeostasis. POP is yet another key target protein for neurodegenerative disorders. The study evaluated peptide libraries of buffalo colostrum whey and fat globule membrane proteins derived from pepsin and pepsin–pancreatin digestion through in silico web tools and structure‐based analysis by molecular docking and binding free‐energy estimation, followed by in vitro assay for DPP‐IV inhibition for the lead peptides. The bioinformatic study indicated 49 peptides presented motifs with DPP‐IV inhibition while 5 peptides with sequences for POP inhibition. In the molecular docking interactions study, 22 peptides interacted with active site residues of DPP‐IV and 3 peptides with that of POP. The synthesized peptides, SFVSEVPEL and LTFQHNF inhibited DPP‐IV in vitro with an IC50 of 193.5 μM and 1.782 mM, respectively. The study revealed the key residues for inhibition of DPP‐IV and POP thus affirming the DPP‐IV inhibitory potential of milk‐derived peptides.