School of Marine Sciences, Ningbo University, Ningbo 315211, China.
Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Mar Drugs. 2019 Mar 19;17(3):179. doi: 10.3390/md17030179.
Angiotensin I-converting enzyme (ACE) inhibitory peptides derived from seaweed represent a potential source of new antihypertensive. The aim of this study was to isolate and purify ACE inhibitory peptides (ACEIPs) from the protein hydrolysate of the marine macroalga . protein was hydrolyzed by five different proteases (trypsin, pepsin, papain, α-chymotrypsin, alcalase) to prepare peptides; compared with other hydrolysates, the trypsin hydrolysates exhibited the highest ACE inhibitory activity. The hydrolysis conditions were further optimized by response surface methodology (RSM), and the optimum conditions were as follows: pH 8.4, temperature 28.5 °C, enzyme/protein ratio (E/S) 4.0%, substrate concentration 15 mg/mL, and enzymolysis time 5.0 h. After fractionation and purification by ultrafiltration, gel exclusion chromatography and reverse-phase high-performance liquid chromatography, two novel purified ACE inhibitors with IC values of 219.35 μM (0.183 mg/mL) and 236.85 μM (0.179 mg/mL) were obtained. The molecular mass and amino acid sequence of the ACE inhibitory peptides were identified as Phe-Gly-Met-Pro-Leu-Asp-Arg (FGMPLDR; MW 834.41 Da) and Met-Glu-Leu-Val-Leu-Arg (MELVLR; MW 759.43 Da) by ultra-performance liquid chromatography-tandem mass spectrometry. A molecular docking study revealed that the ACE inhibitory activities of the peptides were mainly attributable to the hydrogen bond and Zn(II) interactions between the peptides and ACE. The results of this study provide a theoretical basis for the high-valued application of and the development of food-derived ACE inhibitory peptides.
从海藻中提取的血管紧张素转化酶（ACE）抑制肽是一种有潜力的新型抗高血压药物来源。本研究旨在从海洋大型藻类 蛋白质水解物中分离和纯化 ACE 抑制肽（ACEIPs）。使用五种不同的蛋白酶（胰蛋白酶、胃蛋白酶、木瓜蛋白酶、α-糜蛋白酶、碱性蛋白酶）水解 蛋白质制备肽；与其他水解物相比，胰蛋白酶水解物表现出最高的 ACE 抑制活性。通过响应面法（RSM）进一步优化水解条件，最佳条件为：pH8.4、温度 28.5°C、酶/蛋白质比（E/S）4.0%、底物浓度 15mg/mL、酶解时间 5.0h。经过超滤、凝胶排阻色谱和反相高效液相色谱分离和纯化，得到两种新型纯化 ACE 抑制剂，IC 值分别为 219.35 μM（0.183mg/mL）和 236.85 μM（0.179mg/mL）。ACE 抑制肽的分子量和氨基酸序列通过超高效液相色谱-串联质谱鉴定为 Phe-Gly-Met-Pro-Leu-Asp-Arg（FGMPLDR；MW834.41Da）和 Met-Glu-Leu-Val-Leu-Arg（MELVLR；MW759.43Da）。分子对接研究表明，肽的 ACE 抑制活性主要归因于肽与 ACE 之间的氢键和 Zn（II）相互作用。本研究结果为 的高值化应用和食源 ACE 抑制肽的开发提供了理论依据。
