Production and identification of dipeptidyl peptidase IV (DPP-IV) inhibitory peptides from discarded cowhide collagen

[Display omitted] •Double enzymatic hydrolysis combined with IL-US improved DPP-IV inhibitory activity.•IL-US pretreatment induced the exposure of active sites and hydrophobic amino acids.•IL-US pretreatment enhanced the gastrointestinal stability of collagen peptides.•Five new antidiabetic peptides were identified via LC-MS/MS and molecular docking.•The identified GPVGPPG sequence might be the most effective DPP-IV inhibitor. The present study focused on the effects of different preparation conditions on the activity and peptide sequence identification of DPP-IV inhibitory peptides based on discarded cowhide collagen and its regulation mechanism. The highest DPP-IV inhibitory activity (IC50 of 3.04 ± 0.13 mg/mL) was obtained by the combination of double enzymatic hydrolysis (papain and compound protease) and optimized IL-US (ultrasound-assisted ionic liquids) pretreatment. The optimal pretreatment condition for ultrasonic power, ultrasonic time, ionic liquid/collagen ratio, and collagen concentration were 389 W, 25 min, 0.7, and 0.3 %, respectively. IL-US pretreatment induced the exposure of active sites and hydrophobic amino acids of collagen peptide, promoted the partial transformation of β-sheet to β-turn, and enhanced the stability of gastrointestinal digestion. Seven new peptides with DPP-IV inhibitory ability were identified. Importantly, further molecular docking showed that five peptides (GPVG, FGPGP, APGGAP, GPPGPT, and GPVGPPG) were proposed to be antidiabetic peptides from cowhide collagens.