Screening of Angiotensin-I Converting Enzyme Inhibitory Peptides Derived from Caulerpa lentillifera.

Cesarea Joel,Jui-Hsin Su,Jue-Liang Hsu,Arief Prajitno,Christoper Sutopo

doi:10.3390/molecules23113005

Abstract

Peptides with angiotensin-I converting enzyme (ACE) inhibitory activity have received considerable interest due to their potential as antihypertensive agents and consumer concern over the safety of synthetic drugs. The objective of this study was to isolate ACE inhibitory (ACEI) peptides from Caulerpa lentillifera (known commonly as sea grape) protein hydrolysate. In this study, short-chain peptides were obtained after hydrolysis by various enzymes and subsequently by ultrafiltration. Thermolysin hydrolysate showed the highest ACEI activity. Bioassay-guided fractionation was performed using reversed-phase high performance liquid chromatography (RP-HPLC) to uncover the fraction 9 with the highest ACE inhibitory activity from thermolysin hydrolysate. Peptides in this fraction were further identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis coupled with de novo sequencing, which gave two oligopeptides, FDGIP (FP-5) and AIDPVRA (AA-7). The identities and activities of these two peptides were further confirmed using synthetic peptides. Their IC50 values were determined as 58.89 ± 0.68 µM and 65.76 ± 0.92 µM, respectively. Moreover, the inhibition kinetics revealed that both FP-5 and AA-7 are competitive inhibitors. These activities were further explained using molecular docking simulation. The present study is the first report about ACEI peptides derived from Caulerpa lentillifera and it shows the potential for preventing hypertension and for functional food development.

Highlights

Elevated blood pressure, known as hypertension, is an important and controllable cause of cardiovascular disease (CVD) [1]
Our results showed that the inhibition activity (%) for amino acid (AA)-7
The ACE inhibitory (ACEI) peptides FP-5 and AA-7 were simultaneously identified from this ACEI fraction using LC-mass spectrometry (MS)/MS analysis and de novo sequencing

Summary

Introduction

Known as hypertension, is an important and controllable cause of cardiovascular disease (CVD) [1]. Multiple clinical trials have demonstrated the efficacy of angiotensin-I converting enzyme (ACE) inhibitors in controlling blood pressure in hypertensive patients, especially for those with high-risk CVD [3]. Angiotensin-I converting enzyme is a zinc peptidase that plays a major role in the renin-angiotensin system, a system that regulates blood pressure and water balance [4]. Angiotensin-I converting enzyme inhibitors are widely used in the treatment of hypertension by inhibiting the ACE, responsible for the conversion of angiotensin I to the strong vasoconstrictor octapeptide angiotensin II. The two effects together caused by ACE inhibitors result in a relief of hypertension. ACE inhibition has been proven to be an effective therapeutic target for prevention and treatment of hypertension [5]

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