Enzymatically stable renin inhibitors containing statine and 6 aminohexanoic acid. Part IV.
Eight new peptide renin inhibitors: Boc-Phe/4-OMe/His-Sta-epsilonAhx-Iaa(13), Boc-Phe/4-OMe/-His-Sta-episilonAhx-OMe,(21),Boc-Phe/4-OMe/-MePhe-S ta-epsilonAhx-Iaa(27),Boc-Phe/4-OMe/-MePhe-Sta-epsilonAhx-++ +epsilonAhx-Iaa(32),Boc-Phe/4-OMe/-MePhe-Sta-Val-epsilonAhx- OMe (38),Boc-Phe/4-OMe/-MeVal-Sta-Val-Iaa(48),Boc-Phe/4-OMe/-Me Val-Sta-Iaa(51), Boc-Phe/4-OMe/-MeLeu-Sta-epsilonAhx-Iaa (57) have been synthesized in search after compounds of improved biological properties. All peptides were obtained by carbodimide method in solution by stepwise elongation of the peptide chain or by fragment condensation. 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 resistance to enzymatic degradation was assayed by determination of stability to chymotrypsin activity. The most potent inhibitor was (13):IC50 = 7 x 10(-8)M/1. All inhibitors were stable to chymotrypsin.
Paruszewski
R
R
Department of Pharmaceutical Chemistry, Medical University, Warszawa, Poland.
Jaworski
P
P
Tautt
J
J
Dudkiewicz
J
J
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry*; D015119:Aminocaproic Acid / Q000737:chemistry*; D008969:Molecular Sequence Data; D000092502:Renin Inhibitors
D000596:Amino Acids; D015119:Aminocaproic Acid; D000092502:Renin Inhibitors; C013165:statine