Peptides derived from soy and lupin protein as dipeptidyl-peptidase IV inhibitors: in vitro screening and in silico molecular modeling study

Dipeptidyl peptidase IV (DPP-IV) is a new molecular target correlated with the development of diabetes.1 Soluble DPP-IV is a serine exopeptidase that cleaves Xaa-proline or Xaa-alanine dipeptides from the N-terminus of polypeptides. Among all DPP-IV substrates, the most widely investigated are glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), two incretins playing an essential role in maintaining glucose homeostasis.2,3 There are scattered indications in literature that some food peptides may act as inhibitors of this enzyme. We have recently investigated the potential activities of six peptides identified in soybean and lupin protein hydrolyzates, i.e Soy1 (IAVPTGVA), Soy2 (YVVNPDNDEN), Soy3 (YVVNPDNNEN), Lup1 (LTFPGSAED), Lup2 (LILPKHSDAD), and Lup3 (GQEQSHQDEGVIVR), by using an in vitro bioassay against human recombinant DPP-IV. We sorted out two bioactive peptides: Soy1 and Lup1 showed dose-dependent inhibitory effects with IC50 values of 106 and 228 μM, respectively. A molecular docking analysis predicted the key molecular interactions, which stabilize the active peptides within the DPP-IV active site. The results suggest that these DPP-IV inhibitory peptides could be potential ingredients for functional foods or nutraceuticals against type 2 diabetes.