{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:19:46Z","timestamp":1790619586051,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2018,8,4]],"date-time":"2018-08-04T00:00:00Z","timestamp":1533340800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Qingdao Science and Technology Development Project","award":["17-3-3-46-nsh"],"award-info":[{"award-number":["17-3-3-46-nsh"]}]},{"name":"Shandong Provincial Key R &amp; D Program","award":["2017GHY15128"],"award-info":[{"award-number":["2017GHY15128"]}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2015CM011"],"award-info":[{"award-number":["ZR2015CM011"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>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 \u00b1 0.24 and 13.16 \u00b1 0.39 \u03bcM 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.<\/jats:p>","DOI":"10.3390\/md16080271","type":"journal-article","created":{"date-parts":[[2018,8,7]],"date-time":"2018-08-07T03:44:18Z","timestamp":1533613458000},"page":"271","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Novel Natural Angiotensin Converting Enzyme (ACE)-Inhibitory Peptides Derived from Sea Cucumber-Modified Hydrolysates by Adding Exogenous Proline and a Study of Their Structure\u2013Activity Relationship"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7000-5371","authenticated-orcid":false,"given":"Jianpeng","family":"Li","sequence":"first","affiliation":[{"name":"College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zunying","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanhui","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rilei","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyuan","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haohao","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1038\/nrcardio.2017.189","article-title":"Effects of stress on the development and progression of cardiovascular disease","volume":"15","author":"Steptoe","year":"2018","journal-title":"Nat. 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