Exploration of inhibitor effect of Gly-Pro (GP), Arg-Gly-Asp-Ser (RGDS) and Ser-Asp-Gly-Arg-Gly (SDGRG) bioactive peptides on angiotensin-converting enzyme activity purified from human serum.

Abstract

Bioactive peptides (BPs) are a natural and important alternative to synthetic angiotensin-converting enzyme (ACE) inhibitors used in the treatment of hypertension. In this study, ACE was 3575-fold purified from human serum with the affinity chromatography process in one step. The molecular weight and purity of ACE were identified using the SDS-PAGE process and seen in two bands at around 60 kDa and 70 kDa on the gel. Vmax and KM values from the Lineweaver-Burk graphic were determined as 96.15 (µmol/min) mL-1 and 0.2 mM, respectively. The effects of Gly-Pro (GP), Arg-Gly-Asp-Ser (RGDS) and Ser-Asp-Gly-Arg-Gly (SDGRG) BPs on purified ACE were researched. Also, lisinopril was used as a reference inhibitor. GP, RGDS and SDGRG on purified ACE demonstrated an inhibitory effect. IC50 values for these peptides were found as 184.71, 107.16 and 32.54 µM, respectively. Ki values and type of inhibitory for GP, RGDS and SDGRG by the Lineweaver-Burk chart were found. The type of inhibitory for these peptides was calculated as reversible-competitive inhibitory. Ki values for GP, RGDS and SDGRG were calculated to be 260.02, 63.44 and 11.42 µM, respectively. Also, the SDGRG indicated a higher inhibition effect on ACE activity than the GP and RGDS. The IC50 value of lisinopril was designated as 0.35 nM. The inhibition type of lisinopril was designated as reversible noncompetitive inhibition from the Lineweaver-Burk chart and the Ki value was 0.15 nM. Herein, it was concluded that GP, RGDS and SDGRG have ACE inhibitor potential.Communicated by Ramaswamy H. Sarma.