ACE抑制肽构效关系的研究进展及乳源性ACE抑制肽的加工利用现状

对ACE抑制肽的降压机理、构效关系及乳源性ACE抑制肽的加工利用现状等方面进行了介绍。在人体血压调节方面,血管紧张素转换酶(ACE)起着重要的生理作用,越来越多的天然食品源ACE抑制肽被研究和开发利用。本文主要对ACE抑制肽的降压机理、结构、定性/定量构效关系及乳源性ACE抑制肽的加工利用现状等方面进行了综述介绍,以期更好的获得和人工合成优良的ACE抑制肽产品。结果表明,ACE抑制肽的活性与其分子大小、氨基酸种类、序列结构以及空间构象等都密切相关,乳源性的ACE抑制肽的产品在国外已日渐成熟。     

微生物发酵法制备乳源性ACE抑制肽的研究新进展

近年来,对乳源性ACE抑制肽[AngiotensinI-ConvertingEnzyme(ACE)inhibitorypeptides]的研究已成为了一个新的热点。由于它可以降低血压,并且具有安全性、保健性,所以可被广泛地应用于功能性食品市场。旨在促进ACE肽在我国的研究开发,综述了微生物发酵法制备乳源性ACE抑制肽的国内外研究现状,同时较系统地讨论了发酵法制备乳源性ACE抑制肽应注意的几个问题,及对其应用前景进行了展望。     

乳源ACE抑制肽的开发与应用

血管紧张素转化酶(ACE)在血压调节方面起重要作用,目前已从乳蛋白中分离出多种ACE 抑制肽。本文对ACE 抑制肽的作用机理和来源进行介绍,并对乳源ACE 抑制肽的获得与开发及其应用进行综述。     

乳源ACE抑制剂(降血压肽)的研究现状

利用酶或微生物水解牛乳蛋白质可获得ACE抑制剂 (降血压肽 ) ,近来从乳酸菌发酵的酸奶中也找到了ACE抑制肽 ;经动物实验证明 ,口服一定量的ACE抑制肽或含有ACE抑制肽的酸奶可降低血压 ,而且对血压正常者没有影响。文章中综述了来源于乳蛋白质和发酵乳制品的ACE降血压肽的最新研究进展 ,对乳源ACE抑制剂的应用前景进行了展望     

食源性血管紧张素转化酶抑制肽的研究进展

食源性血管紧张素转化酶抑制肽是源于食物蛋白的生物活性小肽,它通过抑制生物体内ACE的活性而发挥出显著的降血压效果,并具有安全性高、无副作用、降压效果温和专一等优点,已成为目前国内外的研究热点。主要从食源性ACE抑制肽的降压机理、ACE抑制肽的定性/定量构效关系、肽的活性与降血压的关系等方面进行了详细综述和归纳。     

ACE抑制肽构效关系研究进展

血管紧张素转化酶(angiotensin-converting enzyme,ACE)抑制肽是一类从食源性蛋白质中分离得到的具有降高血压活性的多肽。由于其降血压效果好,而且没有降压药物的毒副作用从而引起了广泛关注。近年来,ACE抑制肽的构效关系研究成为研究重点。结构生物信息学研究表明,ACE抑制肽的ACE抑制能力不仅与其分子质量有关,而且与其氨基酸序列以及其立体空间构象之间存在高度相关性。ACE抑制肽的抑制类型与ACE抑制活性、构效关系也存在一定相关性。对ACE抑制肽构效关系进行深入研究将有助于指导开发高活性的功能性食品及降血压药物。     

泥鳅ACE抑制肽的体外活性研究

以泥鳅蛋白为原料,酶解制备具有降血压活性的短肽,研究该肽的稳定性。在加热温度≤80℃条件下加热2h,泥鳅降血压肽(<2.5ku)的ACE抑制活性没有显著变化。当2.0≤pH≤8.0时,泥鳅降血压肽的ACE抑制活性变化不显著。冷冻干燥优于喷雾干燥。Mg2+对泥鳅降压肽的降压活性起到促进作用,而Zn2+和Mn2+抑制了肽的降压活性。葡萄糖对降压肽活性的影响程度明显大于蔗糖,随着浓度的升高,其ACE抑制活性逐渐降低,褐变程度加深;氯化钠对降压活性的影响不明显。在模拟胃肠道消化体系中,胃蛋白酶的消化显著提高了产物的降压活性;胰酶的消化降低了产物的降压活性。泥鳅多肽属于底物型ACE抑制肽。     

基于定量构效关系制备火麻仁蛋白ACE抑制肽

高血压是引发心血管疾病的主要因素,经常服用降压的药物会产生副作用,因而安全、高效的食源性降压肽成为关注点。本研究建立了血管紧张素转换酶(ACE)抑制肽的定量构效关系(QSAR)模型,确定ACE抑制肽的结构与其活性间的关系。将模型结果辅以计算机虚拟酶切精确掌握蛋白水解位点,筛选合适的蛋白酶水解火麻仁蛋白定向制备ACE抑制肽,并测定最终水解物的抑制效果。结果表明：基于二肽建立的SVM-AAindex模型具有最佳的预测性能(R²为0.81,RMSE为0.53),且当二肽C端氨基酸为疏水性和芳香族氨基酸时具有较强的ACE抑制效果。蛋白质组分分析发现火麻仁蛋白含有34.60%的疏水性氨基酸和芳香族氨基酸是制备ACE抑制肽的良好来源。选择虚拟酶切产生较多短肽和生物活性肽的碱性蛋白酶和枯草杆菌蛋白酶对火麻仁蛋白进行定向水解,获得的最终水解液的ACE抑制IC50值分别为1.89和2.30 mg/mL。本研究建立了一种高效精准的制备火麻仁蛋白ACE抑制肽的方法,在降血压药物上具有很好的应用前景。     

大豆蛋白源ACE抑制肽研究进展

综述了食源性血管紧张素转化酶(Angiotensin I-converting enzyme,ACE)抑制肽降压机制,大豆蛋白的组成,大豆蛋白源ACE抑制肽的制备和研究进展,以期为大豆蛋白源的ACE抑制肽的进一步研究和开发提供参考。     

瑞士乳杆菌发酵乳制备ACE 抑制肽的条件优化

本研究以脱脂乳为主要原料,对瑞士乳杆菌发酵产生血管紧张素转化酶(angiotensin I-converting enzyme,ACE)抑制肽工艺条件进行研究。通过单因素试验和响应面试验设计,确定瑞士乳杆菌发酵脱脂乳生产ACE 抑制肽的最佳工艺条件为：脱脂乳浓度9.67%(m/V)、底物灭菌时间30min、接种量3%(V/V),温度38.82℃、发酵时间6.26h,测得ACE 抑制率为92.26%。研究结果证实利用发酵法生产乳源ACE 抑制活性肽对控制高血压具有重要意义。     

ACE抑制肽的研究进展

随着高血压患者的大幅增加和人们对健康的重视,血管紧张素转换酶（ACE）抑制肽作为有效的降血压多肽,又因无毒副作用,使其成为近些年的研究热点。文章综述了ACE抑制肽的作用机理和研究历史,从植物及动物方面介绍了多肽的来源,并阐述了直接酶解法、发酵法、固相合成法制备ACE抑制肽方法,以及从体外活性检测和体内活性检测介绍ACE抑制肽检测方法,希望为ACE抑制肽的深入研究提供依据。     

Physiological,chemical and technological aspects of milk-protein-derived peptides with antihypertensive and ACE-inhibitory activity

Among the bioactive peptides derived from milk proteins, those with blood pressure-lowering effects are receiving special attention due to the prevalence and importance of hypertension in the Western population. A few antihypertensive products based on milk-protein-derived peptides with clinically proven health benefits already exist. This paper reviews the current literature on milk-derived peptides with antihypertensive effects. The structure-activity characteristics of angiotensin converting enzyme (ACE) inhibitory peptides are discussed, as well as their bioavailability, potential physiological affects and the existence of mechanisms of action other than ACE inhibition. The paper also focuses on the technological aspects of the production of bioactive dairy products with antihypertensive peptides, either by fermentation with selected microorganisms or by in vitro-hydrolysis and enrichment. Finally, the stability of the peptides during production and processing is addressed, including the potential interactions with other food components and their influence on peptide bioactivity and bioavailability.     

海洋生物来源血管紧张素转换酶抑制肽的研究进展

血管紧张素转化酶(angiotensin converting enzyme,ACE)抑制剂通过抑制ACE活性能够降低血压。目前人工合成ACE抑制药物已开发并应用到降血压的治疗中,但会带来多种副作用。食源性ACE抑制肽与合成抑制剂相比因其副作用小、安全性高等特点,成为ACE抑制肽研究的热点。由于独特的生活环境与巨大的存在数量,海洋生物具有与陆地生物截然不同的化学结构及丰富的生物活性成分。海洋生物来源ACE抑制肽的研究为食源性ACE抑制肽的筛选提供了基础。本文结合海洋生物来源ACE抑制肽的作用机制及制备流程,对鱼类、软体动物、虾类、藻类及海绵、海蜇、粗刺参等不同生物来源的ACE抑制肽制备工艺进行了综述,并对海洋生物的综合开发利用进行了概括。     

血管紧张素转换酶抑制肽定量构效关系研究进展

在血压调节方面,血管紧张素转换酶（ACE）的活性是重要的影响因子。ACE抑制肽具有抑制ACE活性、降低血压等作用。其毒副作用小、安全性高。该文主要对血压调节机制、ACE抑制肽的降压机理、食源性ACE抑制肽的制备以及定量构效关系进行综述介绍,对指导ACE抑制肽的分子设计过程给予理论分析,有望开发出高活性的功能性食品及降血压药物。     

Inhibitory effect of αS1- and αS2-casein hydrolysates on angiotensin I-converting enzyme in human endothelial cells in vitro, rat aortic tissue ex vivo, and renovascular hypertensive rats in vivo

A great number of milk-derived peptides have been shown to exhibit angiotensin converting enzyme (ACE) inhibitory properties and thus potential utility in the regulation of blood pressure. The present work aimed to investigate the effects of 2 milk trypsin hydrolysates from α_S1- and α_S2-casein (CH1 and CH2, respectively) on ACE activity evaluated in human umbilical vein endothelial cells (HUVEC) in vitro, rat aortic tissues ex vivo, and renovascular hypertensive rat in vivo. Incubation of HUVEC and rat aortic tissues with CH1 or CH2 induced a concentration-dependent inhibition of hydrolysis of the ACE substrate hippuryl-histidyl-leucine (HHL), the hydrolysates being much less potent than perindopril (an ACE inhibitor). However, in contrast to perindopril, CH1 and CH2 failed to modify angiotensin I-induced aortic ring vasoconstriction. The HPLC profiles of rat plasma after intragastric administration were variable among individuals but none of the observed peaks corresponded to peptides comprising CH1 or CH2 or to fragments of these peptides. During 4 wk of cardiovascular monitoring, in hydrolysate-fed renovascular hypertensive rats, systolic blood pressure weakly decreased compared with the control group. However, the CH1-fed hypertensive rats exhibited a decrease of heart rate during the nocturnal period of activity. To conclude, our results show that CH1 and CH2 inhibited ACE activity in HUVEC and rat aortic tissue but failed to antagonize the aortic-constricting effects of the natural agonist angiotensin I. Moreover, we demonstrated that CH1, to a greater extent than CH2, can slightly affect cardiovascular parameters although the ingested bioactive peptides could not be detected in the blood.     

Expression of milk-derived angiotensin I-converting enzyme-inhibitory peptides in Lactococcus lactis

Angiotensin I-converting enzyme (ACE) plays a key role in the regulation of blood pressure. Currently, most single or tandem repeats of ACE-inhibitory (ACE-I) peptides have been expressed in Escherichia coli. However, in this study, a food-grade system was constructed using Lactococcus lactis (L. lactis) to simultaneously express four different milk-derived ACE-I peptides with antihypertensive activity. Mixed peptides (MPs) fused with green fluorescent protein (GFP) and eight histidines were synthesized. To ensure potent ACE inhibition by the MPs in human digestive juice, pepsin and trypsin cleavage sites were introduced among the four ACE-I peptides. The MP fusion gene was inserted into expression vector pSEC-E7 with nisin induction and expressed in L. lactis NZ9000, then purified by affinity chromatography. The transformants containing pSEC-MP:GFP were identified based on green fluorescence using Leica laser scanning confocal microscopy. The target proteins were detected by SDS-PAGE analysis and displayed obvious immunogenicity by western blot. After hydrolysis with digestive enzymes, the IC₅₀ of the MPs was 118.63 μM. These results suggested that multiple milk-derived ACE-I peptides with antihypertensive properties could be produced using a food-grade lactococcal expression system.     

ACE抑制肽的制备及其结构对活性的影响

血管紧张素转化酶（ACE）通过一系列的生理反应,从而起到升高血压的作用,在人体中过量ACE的产生会引起高血压,而生物活性物质ACE抑制肽能够抑制ACE的功能。文章主要综述了ACE抑制肽的主要制备方法及氨基酸序列特点与ACE抑制活性的关系,并阐述了脯氨酸对ACE抑制活性的影响,以及部分氨基酸的结构特点及功能,为今后ACE抑制肽的制备与应用提供参考依据。