Bioactive peptides have been considered effective alternatives for the treatment of type 2 diabetes targeting the dipeptidyl peptidase-IV (DPP-IV). In this study, novel DPP-IV inhibitory peptides were prepared and identified from through two-stage chromatographic purification, peptidomic analysis, screening, and validation. Furthermore, molecular simulation was employed to analyze the interaction from a molecular perspective. Results showed that hydrolysate produced by 8 h Neutrase hydrolysis exhibited the significant DPP-IV inhibitory activity. Purification and identification led to the discovery of 387 peptide sequences. A total of 11 novel peptides with potential DPP-IV inhibitory activity were screened . Further synthesis and validation of peptide activity showed that LTWR and DPF significantly inhibit DPP-IV in a competitive inhibitory manner, with IC values of 1788.67 ± 28.13 and 1399.73 ± 27.15 μM, respectively. Results from molecular docking and dynamic simulations indicated that peptides LTWR and DPF could tightly bind to the catalytic site of DPP-IV through hydrogen-bond and hydrophobic interaction. These findings suggested that could serve as a natural source of bioactive peptides for potential treatment of type 2 diabetes.

中文翻译：

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Musculus senhousei 中新型 DPP-IV 抑制肽的制备和鉴定：肽组学分析、分子模拟和验证

以二肽基肽酶-IV (DPP-IV) 为靶点的生物活性肽被认为是治疗 2 型糖尿病的有效替代品。在本研究中，通过两阶段色谱纯化、肽组分析、筛选和验证，制备并鉴定了新型 DPP-IV 抑制肽。此外，还采用分子模拟从分子角度分析相互作用。结果表明，Neutrase水解8小时产生的水解产物表现出显着的DPP-IV抑制活性。纯化和鉴定导致发现了 387 个肽序列。共筛选出11个具有潜在DPP-IV抑制活性的新型肽。进一步合成和肽活性验证表明，LTWR和DPF以竞争性抑制方式显着抑制DPP-IV，IC值分别为1788.67±28.13和1399.73±27.15μM。分子对接和动力学模拟结果表明，肽LTWR和DPF可以通过氢键和疏水相互作用与DPP-IV的催化位点紧密结合。这些发现表明，它可以作为生物活性肽的天然来源，用于潜在治疗 2 型糖尿病。