Angiotensin I-converting enzyme inhibitors derived from an enzymatic hydrolysate of casein. Part IV Studies on the active site and antihypertensive activity of angiotensin I-converting enzyme inhibitors derived from casein.

Abstract

The fragment-peptides of angiotensin I-converting enzyme inhibitors (CEI12, CEI5 and CEIβ7) derived from an enzymatic hydrolysate of casein were synthesized. Val-Ala-Pro, the C-terminal tripeptide of CEI5 (Phe-Phe-Val-Ala-Pro), exhibited more potent inhibitory activity (I50 = 2.0μm) than CEI5 (I50 = 6.0μm). However, d-Val-Ala-Pro showed lower inhibitory activity (I50 = 550μm). Val-Ala-Pro may be important for the inhibitory activity of CEI5. The C-terminal heptapeptide of CEI12 (Phe-Phe-Val-Ala-Pro-Phe-Pro-Glu-Val-Phe-Gly-Lys) and the short fragments of CEIβ7 (Ala-Val-Pro-Tyr-Pro-Gln-Arg) showed lower inhibitory activities than the full-length peptides.Also, the antihypertensive activity of CEI12 and CEI5 was investigated. CEI12, intravenously administered to anesthetized rats at 14.2 mg/kg, antagonized the rats’ pressor response to angiotensin I.