A Novel Angiotensin-I-Converting Enzyme (ACE) Inhibitory Peptide from Takifugu flavidus

Alcalase, neutral protease, and pepsin were used to hydrolyze the skin of Takifugu flavidus. The T. flavidus hydrolysates (TFHs) with the maximum degree of hydrolysis (DH) and angiotensin-I-converting enzyme (ACE)-inhibitory activity were selected and then ultra-filtered to obtain fractions with components of different molecular weights (MWs) (<1, 1–3, 3–10, 10–50, and >50 kDa). The components with MWs < 1 kDa showed the strongest ACE-inhibitory activity with a half-maximal inhibitory concentration (IC50) of 0.58 mg/mL. Purification and identification using semi-preparative liquid chromatography, Sephadex G-15 gel chromatography, RP-HPLC, and LC–MS/MS yielded one new potential ACE-inhibitory peptide, PPLLFAAL (non-competitive suppression mode; IC50 of 28 μmmol·L−1). Molecular docking and molecular dynamics simulations indicated that the peptides should bind well to ACE and interact with amino acid residues and the zinc ion at the ACE active site. Furthermore, a short-term assay of antihypertensive activity in spontaneously hypertensive rats (SHRs) revealed that PPLLFAAL could significantly decrease the systolic blood pressure (SBP) and diastolic blood pressure (DBP) of SHRs after intravenous administration. These results suggested that PPLLFAAL may have potential applications in functional foods or pharmaceuticals as an antihypertensive agent.

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Identification and Molecular Docking Study of a Novel Angiotensin-I Converting Enzyme Inhibitory Peptide Derived from Enzymatic Hydrolysates of Cyclina sinensis

Marine Drugs ◽

10.3390/md16110411 ◽

2018 ◽

Vol 16 (11) ◽

pp. 411 ◽

Cited By ~ 15

Author(s):

Fangmiao Yu ◽

Zhuangwei Zhang ◽

Liwang Luo ◽

Junxiang Zhu ◽

Fangfang Huang ◽

...

Keyword(s):

Liquid Chromatography ◽

Molecular Docking ◽

Inhibitory Activity ◽

Converting Enzyme ◽

Angiotensin I ◽

Ace Inhibitory Activity ◽

Inhibitory Peptide ◽

Angiotensin I Converting Enzyme ◽

Cyclina Sinensis ◽

Ace Inhibitory

Marine-derived angiotensin-I converting enzyme (ACE) inhibitory peptides have shown potent ACE inhibitory activity with no side effects. In this study, we reported the discovery of a novel ACE-inhibitory peptide derived from trypsin hydrolysates of Cyclina sinensis (CSH). CSH was separated into four different molecular weight (MW) fractions by ultrafiltration. Fraction CSH-I showed the strongest ACE inhibitory activity. A peptide was purified by fast protein liquid chromatography (FPLC) and reversed-phase high-performance liquid chromatography (RP-HPLC) and its sequence was determined to be Trp-Pro-Met-Gly-Phe (WPMGF, 636.75 Da). The Lineweaver-Burk plot showed that WPMGF was a competitive inhibitor of ACE. WPMGF showed a significant degree of stability at varying temperatures, pH, and simulated gastrointestinal environment conditions. We investigated the interaction between this pentapeptide and ACE by means of a flexible molecular docking tool. The results revealed that effective interaction between WPMGF and ACE occurred mainly through hydrogen bonding, hydrophobic interactions, and coordination bonds between WPMGF and Zn(II). In conclusion, our study indicates that a purified extract derived from Cyclina sinensis or the WPMGF peptide could potentially be incorporated in antihypertensive functional foods or dietary supplements.

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A novel angiotensin I-converting enzyme inhibitory peptide derived from the trypsin hydrolysates of salmon bone proteins

PLoS ONE ◽

10.1371/journal.pone.0256595 ◽

2021 ◽

Vol 16 (9) ◽

pp. e0256595

Author(s):

Thanakrit Kaewsahnguan ◽

Sajee Noitang ◽

Papassara Sangtanoo ◽

Piroonporn Srimongkol ◽

Tanatorn Saisavoey ◽

...

Keyword(s):

Response Surface ◽

Inhibitory Activity ◽

Fish Bone ◽

Protein Hydrolysates ◽

Converting Enzyme ◽

Angiotensin I ◽

Ace Inhibitory Activity ◽

Inhibitory Peptide ◽

Angiotensin I Converting Enzyme ◽

Ace Inhibitory

When fish are processed, fish bone becomes a key component of the waste, but to date very few researchers have sought to use fish bone to prepare protein hydrolysates as a means of adding value to the final product. This study, therefore, examines the potential of salmon bone, through an analysis of the benefits of its constituent components, namely fat, moisture, protein, and ash. In particular, the study seeks to optimize the process of enzymatic hydrolysis of salmon bone with trypsin in order to produce angiotensin-I converting enzyme (ACE) inhibitory peptides making use of response surface methodology in combination with central composite design (CCD). Optimum hydrolysis conditions concerning DH (degree of hydrolysis) and ACE-inhibitory activity were initially determined using the response surface model. Having thus determined which of the salmon bone protein hydrolysates (SBPH) offered the greatest level of ACE-inhibitory activity, these SBPH were duly selected to undergo ultrafiltration for further fractionation. It was found that the greatest ACE-inhibitory activity was achieved by the SBPH fraction which had a molecular weight lower than 0.65 kDa. This fraction underwent further purification using RP-HPLC, revealing that the F7 fraction offered the best ACE-inhibitory activity. For ACE inhibition, the ideal peptide in the context of the F7 fraction comprised eight amino acids: Phe-Cys-Leu-Tyr-Glu-Leu-Ala-Arg (FCLYELAR), while analysis of the Lineweaver-Burk plot revealed that the FCLYELAR peptide can serve as an uncompetitive ACE inhibitor. An examination of the molecular docking process showed that the FCLYELAR peptide was primarily able to provide ACE-inhibitory qualities as a consequence of the hydrogen bond interactions taking place between ACE and the peptide. Furthermore, upon isolation form the SBPH, the ACE-inhibitory peptide demonstrated ACE-inhibitory capabilities in vitro, underlining its potential for applications in the food and pharmaceutical sectors.

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Angiotensin I-Converting Enzyme (ACE) Inhibitory Activity of Elk (Cervus elaphus) Velvet Antler

Preventive Nutrition and Food Science ◽

10.3746/jfn.2005.10.3.239 ◽

2005 ◽

Vol 10 (3) ◽

pp. 239-243 ◽

Cited By ~ 3

Author(s):

Rohan Karawita ◽

Pyo-Jam park ◽

Nalin Siriwardhana ◽

Byong-Tae Jeon ◽

Sang-Ho Moon ◽

...

Keyword(s):

Cervus Elaphus ◽

Inhibitory Activity ◽

Converting Enzyme ◽

Angiotensin I ◽

Ace Inhibitory Activity ◽

Angiotensin I Converting Enzyme ◽

Velvet Antler ◽

Ace Inhibitory

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A novel Angiotensin-I-converting enzyme (ACE) inhibitory peptide IAF (Ile-Ala-Phe) from pumpkin seed proteins: in silico screening, inhibitory activity, and molecular mechanisms

European Food Research and Technology ◽

10.1007/s00217-021-03783-1 ◽

2021 ◽

Author(s):

Fuqiang Liang ◽

Yumeng Shi ◽

Jiayi Shi ◽

Tai Zhang ◽

Ran Zhang

Keyword(s):

Molecular Mechanisms ◽

Seed Proteins ◽

Converting Enzyme ◽

Angiotensin I ◽

Inhibitory Peptide ◽

In Silico Screening ◽

Pumpkin Seed ◽

Ace Inhibitory Peptide ◽

Angiotensin I Converting Enzyme ◽

Ace Inhibitory

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Angiotensin I Converting Enzyme (ACE) inhibitory activity and antihypertensive effects of grass carp peptides

Food Science and Biotechnology ◽

10.1007/s10068-014-0226-x ◽

2014 ◽

Vol 23 (5) ◽

pp. 1661-1666 ◽

Cited By ~ 2

Author(s):

Shen Wang ◽

Li-mei Lin ◽

Yong-ning Wu ◽

Min Fang ◽

Ya-qin Yu ◽

...

Keyword(s):

Inhibitory Activity ◽

Grass Carp ◽

Converting Enzyme ◽

Angiotensin I ◽

Ace Inhibitory Activity ◽

Angiotensin I Converting Enzyme ◽

Ace Inhibitory

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Effect of Different Proteases on the Degree of Hydrolysis and Angiotensin I-Converting Enzyme-Inhibitory Activity in Goat and Cow Milk

Biomolecules ◽

10.3390/biom8040101 ◽

2018 ◽

Vol 8 (4) ◽

pp. 101 ◽

Cited By ~ 7

Author(s):

Guowei Shu ◽

Jie Huang ◽

Chunju Bao ◽

Jiangpeng Meng ◽

He Chen ◽

...

Keyword(s):

Inhibitory Activity ◽

Goat Milk ◽

Cow Milk ◽

Degree Of Hydrolysis ◽

Converting Enzyme ◽

Angiotensin I ◽

Ace Inhibitory Activity ◽

Inhibitory Peptides ◽

Angiotensin I Converting Enzyme ◽

Ace Inhibitory

Angiotensin I-converting enzyme (ACE) peptides are bioactive peptides that have important value in terms of research and application in the prevention and treatment of hypertension. While widespread literature is concentrated on casein or whey protein for production of ACE-inhibitory peptides, relatively little information is available on selecting the proper proteases to hydrolyze the protein. In this study, skimmed cow and goat milk were hydrolyzed by four commercial proteases, including alkaline protease, trypsin, bromelain, and papain. Angiotensin I-converting enzyme-inhibitory peptides and degree of hydrolysis (DH) of hydrolysates were measured. Moreover, we compared the difference in ACE-inhibitory activity between cow and goat milk. The results indicated that the DH increased with the increase in hydrolysis time. The alkaline protease-treated hydrolysates exhibited the highest DH value and ACE-inhibitory activity. Additionally, the ACE-inhibitory activity of hydrolysates from goat milk was higher than that of cow milk-derived hydrolysates. Therefore, goat milk is a good source to obtain bioactive peptides with ACE-inhibitory activity, as compared with cow milk. A proper enzyme to produce ACE-inhibitory peptides is important for the development of functional milk products and will provide the theoretical basis for industrial production.

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