Harry Nursten Building, Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, UK.
Harborne Building, School of Biological Sciences, University of Reading, Reading RG6 6AP, UK.
Int J Mol Sci. 2020 Jan 29;21(3):864. doi: 10.3390/ijms21030864.
Several milk/whey derived peptides possess high in vitro angiotensin I-converting enzyme (ACE) inhibitory activity. However, in some cases, poor correlation between the in vitro ACE inhibitory activity and the in vivo antihypertensive activity has been observed. The aim of this study is to gain insight into the structure-activity relationship of peptide sequences present in whey/milk protein hydrolysates with high ACE inhibitory activity, which could lead to a better understanding and prediction of their in vivo antihypertensive activity. The potential interactions between peptides produced from whey proteins, previously reported as high ACE inhibitors such as IPP, LIVTQ, IIAE, LVYPFP, and human ACE were assessed using a molecular docking approach. The results show that peptides IIAE, LIVTQ, and LVYPFP formed strong H bonds with the amino acids Gln 259, His 331, and Thr 358 in the active site of the human ACE. Interestingly, the same residues were found to form strong hydrogen bonds with the ACE inhibitory drug Sampatrilat. Furthermore, peptides IIAE and LVYPFP interacted with the amino acid residues Gln 259 and His 331, respectively, also in common with other ACE-inhibitory drugs such as Captopril, Lisinopril and Elanapril. Additionally, IIAE interacted with the amino acid residue Asp 140 in common with Lisinopril, and LIVTQ interacted with Ala 332 in common with both Lisinopril and Elanapril. The peptides produced naturally from whey by enzymatic hydrolysis interacted with residues of the human ACE in common with potent ACE-inhibitory drugs which suggests that these natural peptides may be potent ACE inhibitors.
几种牛奶/乳清衍生的肽具有很高的体外血管紧张素转化酶 (ACE) 抑制活性。然而，在某些情况下，体外 ACE 抑制活性与体内降压活性之间存在较差的相关性。本研究旨在深入了解具有高 ACE 抑制活性的乳清/乳蛋白水解物中肽序列的构效关系，这可能有助于更好地理解和预测其体内降压活性。使用分子对接方法评估了先前报道的高 ACE 抑制剂如 IPP、LIVTQ、IIAE、LVYPFP 和人 ACE 的乳清蛋白产生的肽之间的潜在相互作用。结果表明，肽 IIAE、LIVTQ 和 LVYPFP 与 ACE 活性部位的氨基酸 Gln259、His331 和 Thr358 形成了强氢键。有趣的是，发现相同的残基与人 ACE 抑制药物 Sampatrilat 形成强氢键。此外，肽 IIAE 和 LVYPFP 分别与氨基酸残基 Gln259 和 His331 相互作用，与其他 ACE 抑制剂如卡托普利、赖诺普利和依那普利也有共同作用。此外，IIAE 与赖诺普利共同作用于氨基酸残基 Asp140，而 LIVTQ 与赖诺普利和依那普利共同作用于氨基酸残基 Ala332。通过酶解从乳清中天然产生的肽与人类 ACE 的残基相互作用，与强效 ACE 抑制剂具有共同作用，这表明这些天然肽可能是强效 ACE 抑制剂。
