Whey-Derived Peptides Interactions with ACE by Molecular Docking as a Potential Predictive Tool of Natural ACE Inhibitors

Abstract

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.

Whey-Derived Peptides at the Heart of the COVID-19 Pandemic

“…Additionally, the S1 subsite of ACE is larger than that of ACE2 [ 70 ]. In our previous work, we provided strong in vitro evidence for the ACE inhibitory activity of peptide sequences IPP, IIAE, LIVTQ, and LVYPFP [ 67 , 68 ]. Although all four peptides have been found to exhibit high ACE inhibitory activity, peptide IIAE formed strong hydrogen bonds with the amino acid residues Gln 259 and Thr 358 in the active site of ACE, in common the ACE inhibitory drug Sampatrilat.…”

“…The well-known antihypertensive peptide Ile-Pro-Pro (IPP), along with some other novel peptide sequences that have structural similarities with the reported ACE inhibitory peptides, such as Leu-Val-Tyr-Pro-Phe-Pro (LVYPFP), Leu-Ile-Val-Thr-Gln (LIVTQ), and Ile-Ile-Ala-Glu (IIAE), was characterized and identified by a combination of chemical characterization (LC/MS; MS/MS) and structure-activity relationship data. These peptides produced naturally from whey by enzymatic hydrolysis interacted with residues of human ACE, in common with potent ACE-inhibitory drugs, such as Sampatrilat, Captopril, Lisinopril, and Elanapril, which suggests that these natural peptides may be potent ACE inhibitors [ 67 , 68 ]. The present study aims to explore the efficacy of a natural therapeutic strategy that targets both RAS axes for potential treatment and/or prevention of COVID-19.…”

Novel Angiotensin-I Converting Enzyme Inhibitory Peptides Isolated From Rice Wine Lees: Purification, Characterization, and Structure-Activity Relationship

“…Several types of antihypertensive drugs have been developed based on different therapeutic targets, including angiotensin-I converting enzyme (ACE) inhibitors (4). Angiotensin-I converting enzyme (dipeptidyl carboxypeptidase, EC 3.4.15.1) is a zinc metallopeptidase that is found in male genital, vascular endothelial, neuro-epithelial, and absorptive epithelial cells (5). Angiotensin-I converting enzyme plays dual roles in the renin-angiotensin system (RAS) to regulate blood pressure by degrading angiotensin-I (Ang I) into angiotensin-II (Ang II), a strong vasopressor.…”

Southeast Asian Medicinal Plants with Angiotensin Converting Enzyme (ACE) Inhibition Properties

“…The binding of angiotensin II to angiotensin II type 1 (AT1) receptor causes contraction of vascular smooth muscle cells leading to increased vascular resistance, and it also stimulates the production of aldosterone in the adrenal cortex which in turn increases renal sodium resorption and potassium secretion. 5 Blocking the ACE enzyme reduces the formation of angiotensin II; increases the number of bradykinin, an endothelium-dependent vasodilator; and also reduces aldosterone secretion, all these lead to a reduction in blood pressure 1,6 and have contributed to the clinical use of ACE inhibitors in managing hypertension.…”