Renin inhibitors containing statine and 6-aminohexanoic acid. Part III.
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).
Paruszewski
R
R
Department of Pharmaceutical Chemistry, Medical Academy, Warszawa, Poland.
Tautt
J
J
Dudkiewicz
J
J
D000596:Amino Acids / Q000737:chemistry* / Q000494:pharmacology; D015119:Aminocaproic Acid / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D006868:Hydrolysis; D009842:Oligopeptides; D013050:Spectrometry, Fluorescence; D000092502:Renin Inhibitors
D000596:Amino Acids; D015119:Aminocaproic Acid; D009842:Oligopeptides; D000092502:Renin Inhibitors; C013165:statine