Rapid Screening of Novel Dipeptidyl Peptidase-4 Inhibitory Peptides from Pea (Pisum sativum L.) Protein Using Peptidomics and Molecular Docking

Pea protein hydrolysates (PPHs) possess good hypoglycemic effects; however, their dipeptidyl peptidase-4 (DPP-4) inhibitory activity is poorly understood, and none of the DPP-4 inhibitory peptides have been identified from PPHs. This paper aims to rapidly screen these peptides from PPHs by combining peptidomics and molecular docking. In this study, 543 peptides were identified by peptidomics, and four peptides (IPYWTY, IPYWT, LPNYN, and LAFPGSS) with DPP-4 half-maximal inhibitory concentration (IC 50 ) values <100 μM were screened for the first time. Significantly, peptide IPYWTY exhibited the most potent DPP-4 inhibitory activity (IC 50 = 11.04 μM) mainly because it formed hydrophobic interactions with the S1 pocket in DPP-4. These results indicated that combining peptidomics and molecular docking is an effective strategy for rapidly screening DPP-4 inhibitory peptides.