Yang Zhizhi, Wang Changrong, Huang Baote, Chen Yihui, Liu Zhiyu, Chen Hongbin, Chen Jicheng
College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
Key Laboratory of Cultivation and High-Value Utilization of Marine Organisms in Fujian Province, Fisheries Research Institute of Fujian, National Research and Development Center for Marine Fish Processing (Xiamen), Xiamen 361013, China.
Molecules. 2024 Mar 3;29(5):1134. doi: 10.3390/molecules29051134.
Food-derived angiotensin-I-converting enzyme (ACE)-inhibitory peptides have gained attention for their potent and safe treatment of hypertensive disorders. However, there are some limitations of conventional methods for preparing ACE-inhibitory peptides. In this study, in silico hydrolysis, the quantitative structure-activity relationship (QSAR) model, LC-MS/MS, inhibition kinetics, and molecular docking were used to investigate the stability, hydrolyzability, in vitro activity, and inhibition mechanism of bioactive peptides during the actual hydrolysis process. Six novel ACE-inhibitory peptides were screened from the protein (P) and had low IC values (from 0.63 ± 0.09 µM to 10.26 ± 0.21 µM), which were close to the results of the QSAR model. After in vitro gastrointestinal simulated digestion activity of IPYADFK, FYEPFM and NWPWMK were found to remain almost unchanged, whereas LYDHLGK, INEMLDTK, and IHFGTTGK were affected by gastrointestinal digestion. Meanwhile, the inhibition kinetics and molecular docking results were consistent in that ACE-inhibitory peptides of different inhibition forms could effectively bind to the active or non-central active centers of ACE through hydrogen bonding. Our proposed method has better reproducibility, accuracy, and higher directivity than previous methods. This study can provide new approaches for the deep processing, identification, and preparation of .
食物来源的血管紧张素转换酶（ACE）抑制肽因其对高血压疾病的有效且安全的治疗作用而受到关注。然而，传统的ACE抑制肽制备方法存在一些局限性。在本研究中，采用计算机模拟水解、定量构效关系（QSAR）模型、液相色谱-串联质谱（LC-MS/MS）、抑制动力学和分子对接等方法，研究了生物活性肽在实际水解过程中的稳定性、可水解性、体外活性和抑制机制。从蛋白质（P）中筛选出6种新型ACE抑制肽，其IC值较低（从0.63±0.09μM到10.26±0.21μM），与QSAR模型的结果相近。经体外胃肠道模拟消化后，发现IPYADFK、FYEPFM和NWPWMK的活性几乎不变，而LYDHLGK、INEMLDTK和IHFGTTGK受到胃肠道消化的影响。同时，抑制动力学和分子对接结果一致，即不同抑制形式的ACE抑制肽可通过氢键有效结合到ACE的活性或非中心活性中心。我们提出的方法比以前的方法具有更好的重现性、准确性和更高的针对性。本研究可为……的深加工、鉴定和制备提供新的途径。
