10.3389/fendo.2018.00329.s001 Alice B. Nongonierma Alice B. Nongonierma Luca Dellafiora Luca Dellafiora Sara Paolella Sara Paolella Gianni Galaverna Gianni Galaverna Pietro Cozzini Pietro Cozzini Richard J. FitzGerald Richard J. FitzGerald presentation_1_In Silico Approaches Applied to the Study of Peptide Analogs of Ile-Pro-Ile in Relation to Their Dipeptidyl Peptidase IV Inhibitory Properties.PDF Frontiers 2018 dipeptidyl peptidase IV inhibition Ile-Pro-Ile (diprotin A) bioactive peptides peptide analogs design of experiments quantitative structure activity relationship molecular docking 2018-06-14 04:10:41 Presentation https://frontiersin.figshare.com/articles/presentation/presentation_1_In_Silico_Approaches_Applied_to_the_Study_of_Peptide_Analogs_of_Ile-Pro-Ile_in_Relation_to_Their_Dipeptidyl_Peptidase_IV_Inhibitory_Properties_PDF/6529472 <p>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 (IC<sub>50</sub>) 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 IC<sub>50</sub> 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.</p>