ABSTRACT
Bioactive peptides have been defined as specific protein fragments that have numerous biological activities. The aim of this study was to introduce three multifunctional peptides. Hence, we used rabbit lung angiotensin converting enzyme (ACE) inhibitor peptide AFKDEDTEEVPFR to prepare two analogous peptides KDEDTEEVP and KDEDTEEVH. ACE inhibitory, antioxidant, and antimicrobial activities of three synthetic peptides were investigated. Among the three peptides, KDEDTEEVP exhibited the highest ACE inhibitory activity with IC50 value of 69.63 ± 2.51 µM. Furthermore, the results of fluorescence spectroscopy and molecular modeling showed that KDEDTEEVP had more affinity to ACE than other peptides. The peptide of KDEDTEEVH showed the strongest antioxidant scavenging capacity on DPPH radicals (EC50 = 135 ± 9.62 µM), hydroxyl radicals (EC50 = 144 ± 8.73 µM), and ABTS radicals (EC50 = 62 ± 4.52%). Moreover, it showed the highest activity in iron-chelating test (EC50 = 226 ± 14.13 µM) and could also effectively inhibit the peroxidation of linoleic acid. The antimicrobial activity results showed that KDEDTEEVH had higher efficiency against Gram-positive than Gram-negative bacteria with MIC values of higher than 205 ± 10.75 µM. Although there was not a direct correlation between ACE inhibitor and antioxidant activity for analogous peptides, both analogous peptides exhibited more efficiency than the mother peptide. Thus, they can be considered as multifunctional peptides and would be beneficial ingredient to be used in food and drug industry.
Subject(s)
Angiotensin-Converting Enzyme Inhibitors/chemistry , Peptides/chemistry , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Lipid Peroxidation , Models, Molecular , Molecular Conformation , Peptides/pharmacology , Peptidyl-Dipeptidase A/chemistry , Peptidyl-Dipeptidase A/metabolism , Rabbits , Spectrum Analysis , Structure-Activity RelationshipABSTRACT
Objective To explore the possible inhibitory potentials and mechanism by Mobola plum (Parinari curatellifolia) seeds crude methanol (CE) and flavonoid-rich (FE) extracts on angiotensin-1-converting enzyme (ACE ). Methods The sensitivity and kinetic model of inhibition of CE and FE on ACE using N-[3-(2-furyl)-acryloyl]-Phe-Gly-Gly as enzyme substrate for ACE was evaluated by Michealis Menten approach. The inhibition mechanism was explored from Lineweaver–Burk model and IC
ABSTRACT
Objective:To explore the possible inhibitory potentials and mechanism by Mobola plum (Parinari curatellifolia) seeds crude methanol (CE) and flavonoid-rich (FE) extracts on angiotensin-1-converting enzyme (ACE I).Methods:The sensitivity and kinetic model of inhibition of CE and FE on ACE I using N-[3-(2-furyl)-acryloyl]-Phe-Gly-Gly as enzyme substrate for ACE I was evaluated by Michealis Menten approach.The inhibition mechanism was explored from LineweaverBurk model and IC50 was determined from Cheng-Prusoff empirical analysis.Results:The IC50 of CE and FE were 13.54 and 39.38 μg/mL,respectively.Both extracts exhibited mixed type inhibition with the inhibitory constant (Ki) of CE was between 0.38 and 0.37 μg/mL while that of FE showed a two-fold increase (1.62 μg/mL and 0.28 μg/mL).FE on ACE I demonstrated positive cooperativity with a Hill's coefficient of 1.89.Conclusions:The study reveals the superior ACE I inhibitory potential of CE over FE and suggest that mixed inhibition pattern of the enzyme might be the underlying mechanism of antihypertensive activity.
