DPP-IV Inhibitory Peptide against In Vitro Gastrointestinal Digestion Derived from Goat’s Milk Protein and Its Activity Enhancement via Amino Acid Substitution

作者：Baoyuan He, Yiran Lian, Haiyan Xue, Yan Zhou, Yi Wei, Jun Ma, Yalin Tan, Yawen Wu · 发表于：Foods · 年份：2024 · DOI：10.3390/foods13172721 · 被引用次数：14 · 研究领域：Protein Hydrolysis and Bioactive Peptides、Digestive system and related health、Infant Nutrition and Health

Goat milk protein can release a variety of bioactive peptides after digestion, while most of them are digested into free amino acids or dipeptides via the GI tract. We investigated the peptide profiles of goat milk protein following in vitro gastrointestinal digestion using LC-MS/MS and identified 683 bioactive peptides, including 105 DPP-IV inhibitory peptides. Among these peptides, ILDKVGINY (IL), derived from β-lactoglobulin, was found to be high in content and resistance to digestion. Herein, we explore the effect of amino acid residue substitution at the second N-terminus on its DPP-IV inhibitory activity. Three 9 polypeptide fragments (peptide IL, IP, and II) were synthesized and subjected to molecular docking and activity analysis. The peptide IL demonstrated the highest affinity for DPP-IV with a binding energy of −8.4 kcal/mol and a moderate IC50 value of 1.431 mg/mL determined based on the Caco-2 cell model. The replacement of specific amino acid residues by Pro and Leu led to an increase in the hydrophobic force interaction between the inhibitor peptide and DPP-IV. The inhibition rates of the three peptides were significantly different (p < 0.05). Peptide II containing an Ile residue instead of Leu resulted in a significant enhancement of DPP-IV inhibitory activity, with an IC50 value of 0.577 mg/mL. The GRAVY changes in the three peptides were consistent with the trend of the inhibitory rates. Therefore, the GRAVY of peptides and branch-chain amino acids should...