Generation and characterization of dipeptidyl peptidase-IV inhibitory peptides from trypsin-hydrolyzed α-lactalbumin-rich whey proteins

Food Chem. 2020 Jul 15:318:126333. doi: 10.1016/j.foodchem.2020.126333. Epub 2020 Feb 1.

Abstract

Dipeptidyl peptidase-IV (DPP-IV) is an enzyme that break down the antidiabetic hormone glucagon-like peptide-1. Therefore, inhibition of DPP-IV could be an effective strategy to treat Type 2 diabetes (T2D). The α-lactalbumin-rich whey protein concentrate was hydrolyzed by trypsin, and the hydrolysates were then fractionated at a semi-preparative scale using a Superdex Gel filtration Chromatography. The peptides were analyzed by using HPLC coupled with tandem mass spectrometry (RP-HPLC-MS/MS), and their Dipeptidyl peptidase-IV inhibitory activity was determined by the enzymatic assay. Among tested fragments, a potent fragment (LDQWLCEKL), with the half-maximal inhibitory concentration (IC50) of 131 μM was obtained. Further analysis shows that the LDQWLCEKL peptide corresponds to the amino acid sequence of f(115-123) in α-lactalbumin. Furthermore, LDQWLCEKL exhibited a typical non-competitive mode of inhibition. The results indicate that α-lactalbumin contains active peptides with DPP-IV inhibitory activity that may be used to prevent and treat T2D.

Keywords: Acetonitrile (PubChem CID: 6342); Bioactive peptides; Dipeptidyl peptidase-IV (DPP-IV); Disodium phosphate (PubChem CID: 24203); Hydrochloric acid (PubChem CID: 313); Mode of inhibition; Monosodium phosphate (PubChem CID: 23672064); Response surface methodology; Sodium hydroxide (PubChem CID: 14798); Trifluoroacetic acid (PubChem CID: 6422); α-Lactalbumin.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chromatography, High Pressure Liquid
  • Dipeptidyl Peptidase 4 / chemistry
  • Dipeptidyl Peptidase 4 / metabolism*
  • Dipeptidyl-Peptidase IV Inhibitors / chemistry*
  • Dipeptidyl-Peptidase IV Inhibitors / metabolism
  • Hydrolysis
  • Inhibitory Concentration 50
  • Kinetics
  • Lactalbumin / chemistry
  • Lactalbumin / metabolism*
  • Peptides / analysis
  • Peptides / chemistry*
  • Peptides / metabolism
  • Tandem Mass Spectrometry
  • Trypsin / metabolism
  • Whey Proteins / metabolism*

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Peptides
  • Whey Proteins
  • Lactalbumin
  • Dipeptidyl Peptidase 4
  • Trypsin