[Synthesis and biological activity of some Val(Ala)-Tyr and Val-Tyr-Tyr peptides].
15B2 and WF-10129, reported as potent angiotensin-converting enzyme inhibitors (ACEI), were used as lead compounds for design of novel ACEI. Some of Val-Tyr-Tyr and Val-Tyr peptides were synthesized and tested for ability to inhibit ACE in vitro and in Vivo. The most potent compound was found to be N-(1-benzoyl-1-carboxymethyl)-L-Alanyl-L-Tyrosine (II5, IC50 = 7.9 x 10(-10) mol/L) which was prepared by the addition of Ala-Tyr to benzoyl-acrylic acid in the presence of triethylamine. The structure-activity relationships were also discussed.
Chen
P L
PL
Division of Medicinal Chemistry, China Pharmaceutical University, Nanjing.
Peng
S X
SX
Yang
Z X
ZX
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004151:Dipeptides / Q000138:chemical synthesis*; D066298:In Vitro Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D000806:Angiotensin-Converting Enzyme Inhibitors; D004151:Dipeptides; C080641:N-(1-benzoyl-1-carboxymethyl)alanyl-tyrosine