Evin G, Cumin F, Ménard J, Corvol P, Fehrentz J A, Seyer R, Castro B
J Hypertens Suppl. 1984 Dec;2(3):S227-9.
Recently the nucleotide sequences of the genes coding for mouse and human renins have been elucidated and the primary structures of the corresponding renin precursors deduced. The existence of a prosegment suggests that renin is biosynthesized as an inactive zymogen prorenin. Three peptides related to the region 11-19 of the mouse submaxillary prosegment have been synthesized and tested as inhibitors of pure mouse renin acting on a synthetic porcine substrate. Inhibition of renin activity was effective, with IC50s in the 10(-6) M range. Butyloxycarbonyl-leucyl-lysyl-lysyl-methionyl-proline methyl ester (15-19) was the most potent inhibitor with a K value of 2.3 X 10(-6) M at 37 degrees C in 0.5 M citrate/phosphate buffer (pH 6.0). Peptides 16-20 and 9-20 of the human renin prosegment and peptides 11-19 and 15-19 of the mouse prosegment were tested on human plasma renin activity and found to be inhibitory, with IC50s of 3 to 5 X 10(-4) M. These results demonstrate that the renin prosegment is a renin inhibitor and support the hypothesis that prorenin is an inactive zymogen.
最近，编码小鼠和人肾素的基因的核苷酸序列已被阐明，相应肾素前体的一级结构也已推导出来。前肽段的存在表明肾素是以无活性的酶原——肾素原的形式进行生物合成的。已经合成了三种与小鼠颌下腺前肽段11 - 19区域相关的肽，并将其作为纯小鼠肾素作用于合成猪底物的抑制剂进行了测试。肾素活性的抑制是有效的，IC50在10^(-6) M范围内。在37℃、0.5 M柠檬酸/磷酸盐缓冲液（pH 6.0）中，丁氧羰基 - 亮氨酰 - 赖氨酰 - 赖氨酰 - 甲硫氨酰 - 脯氨酸甲酯（15 - 19）是最有效的抑制剂，K值为2.3×10^(-6) M。对人肾素前肽段的肽16 - 20和9 - 20以及小鼠前肽段的肽11 - 19和15 - 19进行了人血浆肾素活性测试，发现它们具有抑制作用，IC50为3至5×10^(-4) M。这些结果表明肾素前肽段是一种肾素抑制剂，并支持肾素原是一种无活性酶原的假说。
