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肾素-血管紧张素-醛固酮系统(RAA)是一个多步调节的蛋白水解系统,会产生两个增加醛固酮以及引起升压的肽段:血管紧张素Ⅱ和Ⅲ。阻断RAA环节可达到降压目的。肾素催化的水解反应是RAA蛋白水解的第一步。目前已报道了许多底物类肾素抑制剂。本工作设计和合成了八个肾素抑制剂。以α-氨基-β-羟基苯丙酸和α-氨基-β-羟基异庚酸作为底物过渡态类似物,目的是保留Leu~(10)-Val~(11)取代物(LVR)中已还原的肽键,期望增加抑制剂与肾素的结合。
The renin-angiotensin-aldosterone system (RAA) is a multistep-regulated proteolytic system that produces two peptides that increase aldosterone and cause a boost: angiotensin II and III. Block RAA links can achieve the purpose of reducing pressure. Renin-catalyzed hydrolysis is the first step in proteolysis of RAA. A number of substrate renin inhibitors have been reported so far. This work designed and synthesized eight renin inhibitors. Α-Amino-β-hydroxyphenylpropionic acid and α-amino-β-hydroxyheptanoic acid were used as substrate transition state analogues in order to preserve the structure of Leu ~ (10) -Val ~ (11) Reduced peptide bonds are expected to increase the binding of inhibitors to renin.