Chickpea (Cicer arietinum L.) peptides can inhibit dipeptidyl peptidase IV (DPP-IV), an important type 2 diabetes mellitus therapeutic target. The molecular interactions between the inhibitory peptides and the active site of DPP-IV have not been thoroughly examined, nor have their pharmacokinetic properties. Therefore, the predictions of legumin- and provicilin-derived DPP-IV inhibitory peptides, their molecular interactions with the active site of DPP-IV, and their pharmacokinetic properties were carried out. Ninety-two unique DPP-IV inhibitory peptides were identified. Papain and trypsin were the enzymes with the highest AE (0.0927) and lowest BE (6.8625 × 10-7) values, respectively. Peptide binding energy values ranged from -5.2 to -7.9 kcal/mol. HIS-PHE was the most potent DPP-IV inhibitory peptide and interacts with residues of the active sites S1 (TYR662) and S2 (GLU205/ARG125 (hydrogen bonds: <3.0 Å)), S2 (GLU205/GLU206 (electrostatic interactions: <3.0 Å)), and S2' pocket (PHE357 (hydrophobic interaction: 4.36 Å)). Most peptides showed optimal absorption (76.09%), bioavailability (89.13%), and were non-toxic (97.8%) stable for gastrointestinal digestion (73.9%). Some peptides (60.86%) could also inhibit ACE-I. Chickpea is a source of non-toxic and bioavailable DPP-IV-inhibitory peptides with dual bioactivity. Studies addressing the potential of chickpea peptides as therapeutic or adjunct agents for treating type 2 diabetes are warranted.
Keywords: ADMET; DPP-IV inhibitors; bioactive peptides; chickpea; in silico; molecular docking.