Synthesis of Leu-Lys-Tyr Derivatives and Their Interaction with Angiotensin I Converting Enzyme

Abstract

Leucyl-lysyl-tyrosine (LKY) has been found to be a potent angiotensin I converting enzyme (ACE) inhibitor. Through the measurement of ACE inhibitory activity using LKY analogues, the interaction between tripeptides and the active site of ACE was considered. The most preferential sequence of LKY-like-tripeptides was suggested to be: X₁-X₂-X₃: X₁/Leu>Ile, Val>Phe>Ala: X₂/Lys, Arg>Ala>Orn, Thr, etc.: X₃/Trp, Pro>Tyr>Phe. Furthermore, a series of new LKY-like tripeptides exhibiting potent ACE-inhibitory activities were newly synthesized: LKF (7.1), IKY (9.7), IRP (4.5), VKY (7.2), VKP (2.6) and LKY-OC₂H₅ (12.1) (I₅₀ μmol/l). These tripeptide's sequences are informative for clarifying the types of materials that can be obtained for functional foods having antihypertensive activity by enzymatic hydrolysis of natural proteins.