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 CEI_β7) 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 CEI_β7 (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 14.2mg/kg, antagonized the rats' pressor response to angiotensin I.