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In Silico approaches applied to the study of peptide analogs of ile-pro-ile in relation to their dipeptidyl peptidase IV inhibitory properties
Nongonierma, Alice B.; Dellafiora, Luca; Paolella, Sara; Galaverna, Gianni; Cozzini, Pietro; Fitzgerald, Richard J.
Inhibition of dipeptidyl peptidase IV (DPP-IV) may be exploited to maintain the incretin effect during the postprandial phase. As a result, glycemic regulation and energy homeostasis may be improved. Food protein-derived peptides have been identified as natural agents capable of inhibiting DPP-IV. Ile-Pro-Ile is the most potent DPP-IV inhibitory peptide identified to date. A minimum analog peptide set approach was used to study peptide analogs of Ile-Pro-Ile. The DPP-IV half maximal inhibitory concentration (IC50) values of the 25 peptides evaluated ranged from 3.9 ± 1.0 μM (Ile-Pro-Ile) to 247.0 ± 32.7 μM (Phe-Pro-Phe). The presence of Pro at position 2 of tripeptides was required to achieve high DPP-IV inhibition. Most peptides behaved as competitive inhibitors of DPP-IV with the exception of peptides with a N-terminal Trp, which were mixed-type inhibitors. While possessing the structure of preferred DPP-IV substrates, most peptides studied were particularly stable during 30 min incubation with DPP-IV. Molecular docking revealed that Ile-Pro-Ile and its peptide analogs interacted in a very similar manner with the active site of DPP-IV. In addition, no correlation was found between the Hydropathic INTeraction score and the DPP-IV IC50 values of the peptides studied. This outcome suggests that free energy may not be directly responsible for enzyme inhibition by the peptides. Finally, novel DPP-IV inhibitory peptides were identified using the strategy employed herein. These results may be relevant for the development of food protein-derived peptides with serum glucose lowering and food intake regulatory properties in humans.
Keyword(s): dipeptidyl peptidase IV inhibition; Ile-Pro-Ile (diprotin A); bioactive peptides; peptide analogs; design of experiments; quantitative structure activity relationship; molecular docking
Publication Date:
Type: Journal article
Peer-Reviewed: Yes
Language(s): English
Institution: University of Limerick
Funder(s): Enterprise Ireland
Citation(s): Frontiers in Endocrinology;9;Article 329
Publisher(s): Frontiers Media
First Indexed: 2018-07-05 06:25:29 Last Updated: 2018-07-05 06:25:29