title: Structure activity relationship modelling of milk protein-derived peptides with dipeptidyl peptidase IV (DPP-IV) inhibitory activity.
abstract: Quantitative structure activity type models were developed in an attempt to predict the key features of peptide sequences having dipeptidyl peptidase IV (DPP-IV) inhibitory activity. The models were then employed to help predict the potential of peptides, which are currently reported in the literature to be present in the intestinal tract of humans following milk/dairy product ingestion, to act as inhibitors of DPP-IV. Two models (z- and v-scale) for short (2-5 amino acid residues) bovine milk peptides, behaving as competitive inhibitors of DPP-IV, were developed. The z- and the v-scale models (p<0.05, R(2) of 0.829 and 0.815, respectively) were then applied to 56 milk protein-derived peptides previously reported in the literature to be found in the intestinal tract of humans which possessed a structural feature of DPP-IV inhibitory peptides (P at the N2 position). Ten of these peptides were synthetized and tested for their in vitro DPP-IV inhibitory properties. There was no agreement between the predicted and experimentally determined DPP-IV half maximal inhibitory concentrations (IC50) for the competitive peptide inhibitors. However, the ranking for DPP-IV inhibitory potency of the competitive peptide inhibitors was conserved. Furthermore, potent in vitro DPP-IV inhibitory activity was observed with two peptides, LPVPQ (IC50=43.8±8.8μM) and IPM (IC50=69.5±8.7μM). Peptides present within the gastrointestinal tract of human may have promise for the development of natural DPP-IV inhibitors for the management of serum glucose.
authors.affiliation: Department of Life Sciences and Food for Health Ireland (FHI), University of Limerick, Limerick, Ireland.
authors.forename: Alice B
authors.initials: AB
authors.lastname: Nongonierma
authors.affiliation: Department of Life Sciences and Food for Health Ireland (FHI), University of Limerick, Limerick, Ireland. Electronic address: dick.fitzgerald@ul.ie.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: FitzGerald
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008894:Milk Proteins / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D059748:Proteolysis; D021281:Quantitative Structure-Activity Relationship
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D008894:Milk Proteins; D010446:Peptide Fragments; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
keywords: Bioactive peptides; Dipeptidyl peptidase IV inhibition; Milk proteins; Structure activity modelling