Paruszewski R, Tautt J, Dudkiewicz J
Department of Pharmaceutical Chemistry, Medical Academy, Warszawa, Poland.
Pol J Pharmacol. 1993 Jan-Feb;45(1):75-82.
Five peptide renin inhibitors containing the sequence: Phe-His-Sta-epsilon Ahx (Sta = 4(S)-amino-3(S)-hydroxy-6-methylheptanoic acid, epsilon Ahx = 6-aminohexanoic acid) were synthesized and their potency was assayed in vitro by a spectrofluorometric method (assay of Leu-Val-Tyr-Ser released from N-acetyltetradecapeptide substrate by renin in the presence of an inhibitor). Their stability was tested by assay of Phe and Pro-Phe released after incubation with chymotrypsin. The most potent inhibitor was Boc-Phe-His-Sta-epsilon Ahx-OMe (IC50 = 5 x 10(-9) M/l), the most stable--Boc-Pro-Phe-His-Sta-epsilon Ahx-OMe (resistant to incubation with chymotrypsin for 4 h).
合成了五种含有序列Phe-His-Sta-εAhx的肽类肾素抑制剂（Sta = 4(S)-氨基-3(S)-羟基-6-甲基庚酸，εAhx = 6-氨基己酸），并通过荧光分光光度法在体外测定了它们的效力（在抑制剂存在的情况下，测定肾素从N-乙酰十四肽底物中释放出的Leu-Val-Tyr-Ser）。通过测定与胰凝乳蛋白酶孵育后释放出的Phe和Pro-Phe来测试它们的稳定性。效力最强的抑制剂是Boc-Phe-His-Sta-εAhx-OMe（IC50 = 5×10(-9) M/l），最稳定的是Boc-Pro-Phe-His-Sta-εAhx-OMe（在与胰凝乳蛋白酶孵育4小时后仍具有抗性）。
