Arachin derived peptides as selective angiotensin I-converting enzyme ( ACE) inhibitors: Structure-activity relationship
Arachin derived peptides as selective angiotensin I-converting enzyme ( ACE) inhibitors: Structure-activity relationship
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DOI：
10.1016/j.peptides.2010.02.022
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发表时间：
2010-06-01
期刊：
影响因子：
3
通讯作者：
Gowda, Lalitha R.
中科院分区：
文献类型：
--
作者：
Jimsheena, V. K.;Gowda, Lalitha R.
目前的注意力集中在通过抑制血管紧张素I转化酶（ACE）控制血压的机制上。食品来源的生物活性抗高血压肽作为合成药物在高血压治疗中的替代品越来越重要。花生（Arachis hypogaea）的主要贮藏球蛋白花生素的酶消化物的ACE抑制特性已被证明。从这些植物中分离的三肽（IEY）的ACE抑制活性已被表征。组装了该肽的五种合成结构类似物（IEW、IKY、IKW、IEP和IKP），并评价了它们的ACE抑制活性。其中，三肽IKP是一种有效的竞争性抑制剂，IC 50为7 +/- 1 x 10（-6）M，与有效的乳清肽IPP和VPP相似。这些肽类似物的抑制数据已通过使用tACE-赖诺普利复合物在2埃分辨率下的对接模拟得到合理化（PDB：1086）。最佳对接位姿位于tACE催化位点，类似于合成药物赖诺普利所产生的抑制模式。肽的抑制程度与催化Zn（II）和氨基末端和中间残基之间的肽键的羰基氧之间的配位距离相关。这些研究表明，这些肽，如赖诺普利，表现为过渡态类似物抑制剂，并在血压管理的治疗干预是有用的。(C)2010年爱思唯尔公司All rights reserved.
Current attention focuses on mechanisms of controlling blood pressure through the inhibition of angiotensin I-converting enzyme (ACE). Bioactive antihypertensive peptides of food origin are increasingly gaining importance as alternates to synthetic drugs in hypertension therapy. The ACE inhibitory property of an enzymatic digest of arachin, the major storage globulin of peanut (Arachis hypogaea) has been demonstrated. The ACE inhibitory activity of a tripeptide (IEY) isolated from these digests has been characterized. Five synthetic structural analogs of this peptide (IEW, IKY, IKW, IEP and IKP) were assembled and their ACE inhibitory activity evaluated. Among these, the tripeptide IKP was a potent competitive inhibitor with an IC50 of 7 +/- 1 x 10(-6) M similar to that of the potent whey peptides IPP and VPP. The inhibition data of these peptide analogs have been rationalized through docking simulations using the tACE-lisinopril complex at 2 angstrom resolution (PDB: 1086). The best docking poses were located at the tACE catalytic site resembling the mode of inhibition exerted by lisinopril, the synthetic drug. The degree of inhibition by the peptides correlated with the coordination distance between the catalytic Zn(II) and the carbonyl oxygen of the peptide bond between the amino-terminal and middle residue. These studies illustrate that these peptides, like lisinopril, behave as transition state analog inhibitors and are useful in therapeutic intervention for blood pressure management. (C) 2010 Elsevier Inc. All rights reserved.