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.

Jianpeng Li,Rilei Yu,Shiyuan Dong,Haohao Wu,Yuanhui Zhao,Zunying Liu,Xiaojie Zhu

doi:10.3390/md16080271

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.

Highlights

Hypertension is one of the leading causes of global disease burden [1]
The obtained activity was found in the Pro group (p < 0.05). These results demonstrate that the plastein reaction results are consistent with Sun et al [11], who reported that the Angiotensin-converting enzyme (ACE)-inhibitory activity of casein modified by the addition of exogenous Pro was capable of improving ACE‐inhibitory activity
Our results indicate that PNVA and PNLG are novel ACE-inhibitory peptides, which are peptides,inwhich are realized in Acaudina hydrolysates byPro

Summary

Introduction

Hypertension is one of the leading causes of global disease burden [1]. In 2015, hypertension was estimated to affect 874 million adults worldwide (systolic blood pressure ≥ 140 mmHg), causing approximately 4.5 million deaths. The number of patients suffering from hypertension continues to grow [2]. Angiotensin-converting enzyme (ACE) plays a critical role in blood pressure control systems (renin-angiotensin system) as it converts angiotensin I into angiotensin II, leading to the development of hypertension [3,4]. It is quite essential to study the inhibition of ACE in order to prevent and manage hypertension. Mar. Drugs 2018, 16, 271; doi:10.3390/md16080271 www.mdpi.com/journal/marinedrugs

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