Structure activity relationship modelling of milk protein derived peptides with dipeptidyl peptidase IV (DPP IV) inhibitory activity
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+ 8.8mM) and IPM (IC50=69.5+ 8.7mM) 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.
Peptides