CN108129561B - 一种ace抑制肽 - Google Patents

一种ace抑制肽 Download PDF

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CN108129561B
CN108129561B CN201711348032.0A CN201711348032A CN108129561B CN 108129561 B CN108129561 B CN 108129561B CN 201711348032 A CN201711348032 A CN 201711348032A CN 108129561 B CN108129561 B CN 108129561B
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ace inhibitory
inhibitory peptide
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Abstract

本发明公开了一种ACE抑制肽，所述ACE抑制肽的氨基酸序列为His‑Glu‑Arg(HER)，该肽可有效抑制ACE活性，IC50值为1.82±0.06mM。本发明所涉及的ACE抑制肽具有结构简单、安全、活性强等特点，具有广泛的应用前景。

Description

一种ACE抑制肽
技术领域
本发明涉及生一种血管紧张素转化酶(ACE)抑制肽。
背景技术
大黄鱼又名大黄花，是我国近海主要经济鱼类。其肉质鲜美，营养丰富。肌动蛋白和肌球蛋白是鱼类中的主要肌原纤维蛋白，贡献高达80％的肌原纤维蛋白组分。随着对海洋生物的深入研究，越来越多的生理活性物质被发现，特别是对肽的研究。大黄鱼肽主要功能体现在抗氧化，抗菌等方面。
高血压是一种慢性疾病被称为无形的杀手，对全球约三分之一的成年人造成影响，造成死亡人数占总死亡人数二分之一左右。长期高血压通常被认为是冠状动脉疾病，外周血管疾病，视力丧失和慢性肾病的主要危险因素。
科学研究表明，人体通过肾素-血管紧张素系统(RAS)，激肽原-氧化氮系统(KNOS)，肾素-糜蛋白酶系统(RCS)和中性内肽酶系统(NEPS)等多种生化系统调节血压。血管紧张素转换酶(ACE)在RAS和KNOS调节血压方面起着至关重要的作用，ACE切割血管紧张素-I(ANG I)羧基端的两个氨基酸，将基本无生物失活的ANG I转化为有效的血管收缩剂血管紧张素-II(ANG II)并使血管舒张肽缓激肽失活，因此有效的抑制血管紧张素转换酶(ACE)是控制高血压的切实有效的方法。
临床上通常使用卡托普利，依那普利和赖诺普利等合成药物治疗高血压。但是，这些合成药物具有许多副作用，与合成ACE抑制剂相比，来自天然食物的ACE抑制肽安全性，稳定性更好，副作用更小。因此，科学家将致力于寻找高效的食源性ACE抑制肽。
发明内容
本发明的目的在于提供一种来自大黄鱼肌动蛋白的活性肽，其具有ACE抑制活性，并可将应用于保健食品或药品的研发。
本发明所述的ACE抑制肽，氨基酸序列为His-Glu-Arg(HER)，其分子量为440.459Da，等电点为7.57。
上述本发明的ACE抑制肽序列，包括以所述ACE抑制肽序列为核心，任何对其进行的相应的调整或修饰。
为了实现上述目的，本发明所采用的技术方案是：
本发明借助于虚拟酶解和分子对接等虚拟筛选技术。将大黄鱼肌动蛋白进行虚拟酶切，得到一定量的肽序列，筛选其中未被报道的三肽序列进行毒性、水溶性和ADMET性质的预测，并利用Discovery studio软件进行分子对接，最终筛选得到三肽His-Glu-Arg(HER)。利用RP-HPLC法进行三肽HER体外ACE抑制活性的鉴定。结果显示HER具有良好ACE抑制活性，IC50值为1.82±0.06mM。
本发明的有益效果：
1.从大黄鱼肌动蛋白中筛选得到了具有的ACE抑制活性的肽，其序列为His-Glu-Arg(HER)。HER可有效抑制ACE活性，具有潜在的医学价值。
2.本发明与传统酶解提取的方法相比，具有简单、快速、成本低等特点，可为快速筛选高效的食源性活性肽提供较好的理论指导。
附图说明
本发明附图1幅
图1为HER与ACE的对接结果展示。
具体实施方式
以下结合具体实施例对本发明的具体实施方式作进一步详细说明。
实施例1 大黄鱼肌动蛋白的虚拟酶解及虚拟筛选
1、大黄鱼肌动蛋白中潜在生物活性肽的筛选。
从NCBI数据库中得到大黄鱼肌动蛋白序列(KKF15719)，选用胃蛋白酶、胰蛋白酶、糜蛋白酶对其进行虚拟酶解。未经发表的三肽序列通过ToxinPred和Innovagen服务器进行毒性和水溶性预测以得到具有潜在生物活性的肽序列，得到无毒且具有良好水溶性的三肽序列。
2.潜在ACE抑制肽的筛选
从PDB数据库中，搜寻得到ACE的晶体结构(1O86分辨率2.0
Figure BSA0000155672540000031
)，借助DS设定其为受体蛋白，并预测活性位点以进行分子对接。通过Libdock对步骤1中所得到的三肽序列与ACE进行对接。并计算前十个较优构象的LibDock得分。
3.ADME性质预测
经步骤2Libdock所筛选出的三肽序列，经admetSAR进行ADME性质预测。包括人体小肠吸收(HIA)，血脑屏障(BBB)渗透性，Caco-2渗透性和代谢参数。选择具有最佳药代动力学和药效学性质的三肽进行化学合成并进行体外活性的测定。
实施例2HER体外ACE抑制活性鉴定
采用高效液相色谱法，取马尿酰组胺酰亮氨酸(HHL)底物溶液，加入抑制剂混合均匀，在37℃恒温水浴中预热3～5min，然后加入ACE液充分混合，37℃保温30min后，再加入的1mol/L HCl终止反应，得到反应液。同时用硼酸缓冲液替代抑制剂溶液作为空白对照组。该反应液直接用HPLC系统进行分析。
色谱条件：柱温25℃，流速0.5mL/min，流动相乙腈/水为25∶75等度洗脱，检测波长228nm。
5.结果分析
综合以上所有结果，进行综合评定，筛选得到三肽HER。HER具有良好ACE抑制活性，IC50值为1.82±0.06mM，其与ACE的相互作用结果如附图1所示。
基于上文对本发明的充分理解，申请人相信，本领域技术人员应当容易理解，本发明所述的肽及其相关的衍生产品，都应当属于本发明所涉及范畴。

Claims (1)

1.一种ACE抑制肽在制备具有辅助降血压作用的保健食品中的应用，所述ACE抑制肽的氨基酸序列为HER。
CN201711348032.0A 2017-12-06 2017-12-06 一种ace抑制肽 Expired - Fee Related CN108129561B (zh)

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CN108948143B (zh) * 2018-07-24 2021-06-25 渤海大学 具有ace抑制活性的三肽及其应用
CN114106092B (zh) * 2021-09-29 2023-08-22 重庆师范大学 一种具有ace抑制作用的活性多肽及其应用

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WO2003084477A2 (en) * 2002-03-29 2003-10-16 Centocor, Inc. Mammalian cdr mimetibodies, compositions, methods and uses
CN1890383A (zh) * 2003-09-30 2007-01-03 森托科尔公司 人铰链核心模拟体、组合物、方法和用途

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US6126939A (en) * 1996-09-03 2000-10-03 Yeda Research And Development Co. Ltd. Anti-inflammatory dipeptide and pharmaceutical composition thereof
CN103980347B (zh) * 2014-05-22 2017-05-17 浙江海洋学院 一种大黄鱼鱼鳔降压肽及其制备方法和用途

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WO2003084477A2 (en) * 2002-03-29 2003-10-16 Centocor, Inc. Mammalian cdr mimetibodies, compositions, methods and uses
CN1890383A (zh) * 2003-09-30 2007-01-03 森托科尔公司 人铰链核心模拟体、组合物、方法和用途

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