Collect. Czech. Chem. Commun. 1988, 53, 2591-2598

Peptide inhibitors of the angiotensin converting enzyme with nonproteinogenic amino acids

Siegmund Reissmanna, Carola Schwuchowa, Margarita P. Filatovab, Natalya A. Kritb, Wolf-Eberhard Siemsc, Gottfried Hederc, Uwe Schradera, Harald Schuberta, Bettina Müllera, Bettina Bardla and Inge Paegelowd

a Department of Biology, Friedrich-Schiller-University, 6900 Jena, G.D.R.
b Institute of Biological and Medicinal Chemistry, Academy of Medicinal Sciences, Moscow, U.S.S.R.
c Institute of Drug Research, Academy of Sciences, 1136 Berlin-Friedrichsfelde, G.D.R.
d Institute of Pharmacology and Toxicology, Wilhelm-Pieck-University, 2500 Rostock, G.D.R.


To study the structural requirements of the angiotensin converting enzyme we have synthesized and tested two series of acylated tripeptides with the common structure Acyl-AA1-AA2-Pro and Acyl-AA1-Arg-Pro. The structure-activity relationship indicates that the inhibitory activities result from the structure and conformation of the whole molecule. The use of nonproteinogenic amino acids in the positions AA1 and AA2 stabilizes to some degree the peptides against enzymatic degradation. Some of the acylated tripeptides are able to reduce the angiotensin I-induced blood pressure enhancement of normotensive rats. The peptides are applied orally. No good correlation exist between the inhibitory activity of the isolated enzyme and the in vivo activity. The structural requirements for the inhibition of the isolated ACE and the potentiation of the bradykinin action on the guinea pig ileum are different.