Isolation and characterization of peptides with dipeptidyl peptidase-IV inhibitory activity from pepsin-treated bovine whey proteins.

Publication Type:

Journal Article


Peptides, Volume 54, p.39-48 (2014)


Amino Acid Sequence, Animals, Cattle, Chemical Fractionation, Dipeptidyl-Peptidase IV Inhibitors, Lactalbumin, Lactoglobulins, Milk Proteins, Molecular Sequence Data, Pepsin A, Proteomics Core Facility, Spectrometry, Mass, Electrospray Ionization, Structure-Activity Relationship, Whey Proteins


Inhibition of the enzyme dipeptidyl peptidase (DPP)-IV is one of the strategies used for the treatment of type 2 diabetes. In the present study, pepsin-treated whey protein isolate (WPI) and α-lactalbumin displaying DPP-IV inhibitory activity were fractionated by successive chromatographic steps and the resulting active fractions analyzed for their constituent peptides by liquid chromatography-electrospray ionization-tandem mass spectrometry. Among the identified sequences, 24 peptides derived from α-lactalbumin and 11 from β-lactoglobulin were synthesized and their effects on DPP-IV activity assessed. The most potent fragments, LKPTPEGDL and LKPTPEGDLEIL (IC50=45 and 57 μM, respectively), were found to inhibit DPP-IV in an un-competitive manner. Although several of the peptides tested showed some inhibitory activity, only two were as effective as the un-fractionated WPI hydrolysate and none were as potent as the un-fractionated α-lactalbumin hydrolysate. The peptides' structural features, including length and amino acid composition, were found to impact their inhibitory activity. This study provides new insights on the active components responsible for the DPP-IV inhibitory activity of pepsin-treated whey proteins.