Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
Mar Drugs
2018 Aug 04;168:. doi: 10.3390/md16080271.
Show Gene links
Show Anatomy links
Novel Natural Angiotensin Converting Enzyme (ACE)-Inhibitory Peptides Derived from Sea Cucumber-Modified Hydrolysates by Adding Exogenous Proline and a Study of Their Structure⁻Activity Relationship.
Li J
,
Liu Z
,
Zhao Y
,
Zhu X
,
Yu R
,
Dong S
,
Wu H
.
???displayArticle.abstract???
Natural angiotensin converting enzyme (ACE)-inhibitory peptides, which are derived from marine products, are useful as antihypertensive drugs. Nevertheless, the activities of these natural peptides are relatively low, which limits their applications. The aim of this study was to prepare efficient ACE-inhibitory peptides from sea cucumber-modified hydrolysates by adding exogenous proline according to a facile plastein reaction. When 40% proline (w/w, proline/free amino groups) was added, the modified hydrolysates exhibited higher ACE-inhibitory activity than the original hydrolysates. Among the modified hydrolysates, two novel efficient ACE-inhibitory peptides, which are namely PNVA and PNLG, were purified and identified by a sequential approach combining a sephadex G-15 gel column, reverse-phase high-performance liquid chromatography (RP-HPLC) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS), before we conducted confirmatory studies with synthetic peptides. The ACE-inhibitory activity assay showed that PNVA and PNLG exhibited lower IC50 values of 8.18 ± 0.24 and 13.16 ± 0.39 μM than their corresponding truncated analogs (NVA and NLG), respectively. Molecular docking showed that PNVA and PNLG formed a larger number of hydrogen bonds with ACE than NVA and NLG, while the proline at the N-terminal of peptides can affect the orientation of the binding site of ACE. The method developed in this study may potentially be applied to prepare efficient ACE-inhibitory peptides, which may play a key role in hypertension management.
Figure 1. Effect of different amino acids (A), proline proportions (B) and reaction time (C) on the ACE-inhibitory activity. The values of three replicates are shown as mean ± standard deviation. Different lowercase letters indicate significantly different values (p < 0.05).
Figure 2. Isolation and purification of modified ACE-inhibitory peptides using a Sephadex G-15 gel column (A) and RP-HPLC (B). The corresponding ACE-inhibitory activities of each fraction are shown in (C,D). Different lowercase letters indicate significantly different values (p < 0.05).
Figure 3. MALDI-TOF/MS spectra of the amino acid sequences of fraction E3. (A) peptide PNVA. (B) peptide PNLG.
Figure 4. (A–H) show the binding modes of PNVA, PNLG, NVA and NLG with the ACE, respectively. (B,D,F,H) show 2D schematics of the peptide-binding modes. The dashed lines indicate the hydrogen bonds that were formed between the peptide and residues of the binding sites.
Figure 5. Schematic illustration of the formation of ACE-inhibitory peptides during the plastein reaction.
Abuohashish,
ACE-2/Ang1-7/Mas cascade mediates ACE inhibitor, captopril, protective effects in estrogen-deficient osteoporotic rats.
2017,
Pubmed
Aluko,
Antihypertensive peptides from food proteins.
2015,
Pubmed
Bernstein,
Angiotensin-converting enzyme in innate and adaptive immunity.
2018,
Pubmed
Bougatef,
Angiotensin I-converting enzyme (ACE) inhibitory activities of sardinelle (Sardinella aurita) by-products protein hydrolysates obtained by treatment with microbial and visceral fish serine proteases.
2008,
Pubmed
Charton,
The structural dependence of amino acid hydrophobicity parameters.
1982,
Pubmed
Chen,
Processing Optimization and Characterization of Angiotensin-Ι-Converting Enzyme Inhibitory Peptides from Lizardfish (Synodus macrops) Scale Gelatin.
2018,
Pubmed
Corrons,
ACE-inhibitory peptides from bovine caseins released with peptidases from Maclura pomifera latex.
2017,
Pubmed
Erdmann,
The possible roles of food-derived bioactive peptides in reducing the risk of cardiovascular disease.
2008,
Pubmed
Forouzanfar,
Global Burden of Hypertension and Systolic Blood Pressure of at Least 110 to 115 mm Hg, 1990-2015.
2017,
Pubmed
Ha,
Identification of Antihypertensive Peptides Derived from Low Molecular Weight Casein Hydrolysates Generated during Fermentation by Bifidobacterium longum KACC 91563.
2015,
Pubmed
Kivimäki,
Effects of stress on the development and progression of cardiovascular disease.
2018,
Pubmed
Kleekayai,
Extraction of antioxidant and ACE inhibitory peptides from Thai traditional fermented shrimp pastes.
2015,
Pubmed
Liu,
Characterization of ACE inhibitory peptides from Mactra veneriformis hydrolysate by nano-liquid chromatography electrospray ionization mass spectrometry (Nano-LC-ESI-MS) and molecular docking.
2014,
Pubmed
Ngo,
Active peptides from skate (Okamejei kenojei) skin gelatin diminish angiotensin-I converting enzyme activity and intracellular free radical-mediated oxidation.
2014,
Pubmed
Raia,
Angiotensin-converting enzyme inhibitors: a comparative review.
1990,
Pubmed
Sangsawad,
Transepithelial transport across Caco-2 cell monolayers of angiotensin converting enzyme (ACE) inhibitory peptides derived from simulated in vitro gastrointestinal digestion of cooked chicken muscles.
2018,
Pubmed
Terashima,
Inhibition strength of short peptides derived from an ACE inhibitory peptide.
2011,
Pubmed
Todd,
Relation between changes in blood pressure and serum ACE activity after a single dose of enalapril and ACE genotype in healthy subjects.
1995,
Pubmed
Vilar,
Medicinal chemistry and the molecular operating environment (MOE): application of QSAR and molecular docking to drug discovery.
2008,
Pubmed
Wood,
Bronchospasm and cough as adverse reactions to the ACE inhibitors captopril, enalapril and lisinopril. A controlled retrospective cohort study.
1995,
Pubmed
Yu,
Isolation and characterization of angiotensin I-converting enzyme inhibitory peptides derived from porcine hemoglobin.
2006,
Pubmed
Zhao,
A novel ACE inhibitory peptide isolated from Acaudina molpadioidea hydrolysate.
2009,
Pubmed
,
Echinobase
Zhou,
Molecular mechanism of the interactions between inhibitory tripeptides and angiotensin-converting enzyme.
2012,
Pubmed
