Inhibition of dipeptidyl peptidase IV (DPP-IV) by proline containing casein-derived peptides

Abstract

Dipeptides with a C terminal Pro inhibit dipeptidyl peptidase IV (DPP-IV), a key enzyme in incretin hormone processing. It was hypothesised that tri- and tetrapeptides with a proline at the C-terminus may also be DPP-IV inhibitors. Therefore, an in silico hydrolysis approach was used to release short (4 ⩽ amino acids) C terminal Pro peptides from the individual caseins which constitute Pro rich substrates. This was achieved using theoretical digestion of caseins with a prolyl oligopeptidase activity. Fifteen peptides were subsequently selected for in vitro DPP-IV inhibitory analysis. Stability of these peptides to gastrointestinal enzymes was also evaluated in silico and the predicted breakdown peptides were assessed for their DPP-IV inhibitory and antioxidant potential. New DPP-IV inhibitors were identified, the most potent being Phe-Leu-Gln-Pro (IC50 65.3 ± 3.5 μM). A low in vitro antioxidant (2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging) activity was also associated with the peptides studied. The strategy presented highlights the utility of employing an in silico approach for the prediction of food-derived peptides with a potential role in glycaemic management for subsequent development of functional foods.

Keywords

• Dipeptidyl peptidase IV inhibitors
• Antioxidant
• Bioactive peptides
• Milk
• Proline