Novel peptide inhibitors of angiotensin-converting enzyme 2
Novel peptide inhibitors of angiotensin-converting enzyme 2
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DOI：
10.1074/jbc.m212934200
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发表时间：
2003-05-02
影响因子：
4.8
通讯作者：
Ladner, RC
中科院分区：
文献类型：
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作者：
Huang, LL;Sexton, DJ;Ladner, RC
血管紧张素转换酶 2 (ACE2) 是最近发现的 ACE 的人类同源物，是一种新型金属羧肽酶，其特异性、组织分布和功能均不同于 ACE。 ACE2可能在肾素-血管紧张素系统中发挥独特的作用并介导心血管和肾功能。在这里，我们报告了通过选择噬菌体上展示的受限肽文库发现的 ACE2 肽抑制剂。针对 FLAG 标记的 ACE2 靶标构建并选择了 6 个受限肽库。 ACE2 肽结合剂根据其对 ACE2 活性的影响被鉴定并分为五组。前三类肽对 ACE2 表现出无抑制、弱抑制或中度抑制。第四类肽表现出强烈的抑制作用，平衡抑制常数（K-i 值）为 0.38 至 1.7 gm。第五类肽表现出非常强的抑制作用，K-i 值
Angiotensin-converting enzyme 2 (ACE2), a recently identified human homolog of ACE, is a novel metallocarboxypeptidase with specificity, tissue distribution, and function distinct from those of ACE. ACE2 may play a unique role in the renin-angiotensin system and mediate cardiovascular and renal function. Here we report the discovery of ACE2 peptide inhibitors through selection of constrained peptide libraries displayed on phage. Six constrained peptide libraries were constructed and selected against FLAG-tagged ACE2 target. ACE2 peptide binders were identified and classified into five groups, based on their effects on ACE2 activity. Peptides from the first three classes exhibited none, weak, or mode-rate inhibition on ACE2. Peptides from the fourth class exhibited strong inhibition, with equilibrium inhibition constants (K-i values) from 0.38 to 1.7 gm. Peptides from the fifth class exhibited very strong inhibition, with K-i values