Susceptibility of milk protein-derived peptides to dipeptidyl peptidase IV (DPP-IV) hydrolysis

Abstract

In silico digestion of milk protein-derived peptides with gastrointestinal enzyme activities was used to predict the release of peptides with a Pro residue at position 2 from the N terminus. These peptides are known to act as preferred dipeptidyl peptidase IV (DPP-IV) substrates. Five casein-derived synthetic peptides (Ile-Pro-Ile-Gln-Tyr, Leu-Pro-Leu-Pro-Leu, Tyr-Pro-Tyr-Tyr, Leu-Pro-Tyr-Pro-Tyr and Ile-Pro-Ile) and a casein (CasH), whey (WPH) and lactoferrin hydrolysate (LFH) generated with gastrointestinal enzymes were incubated with DPP-IV at 37 °C for 18 or 24h. Peptide breakdown was evident following incubation with DPP-IV. Different modes of DPP-IV inhibition were observed depending on the test compound. Ile-Pro-Ile-Gln-Tyr, Tyr-Pro-Tyr-Tyr and Leu-Pro-Tyr-Pro-Tyr were substrate-, Leu-Pro-Leu-Pro-Leu and CasH were prodrug- while WPH and LFH were true DPP-IV inhibitors. These results are relevant for the bioactivity and bioavailability of functional foods targeting DPP-IV inhibition with potential blood glucose regulatory properties in humans.

Keywords: Antioxidant; Bioactive peptides; Dipeptidyl peptidase IV inhibitors; Milk; Prodrug-type inhibition; Substrate-type inhibition.