A pivotal peptide (Ile-Leu-Lys-Pro) with high ACE- inhibitory activity from duck egg white: identification and molecular docking

Haitao Li,Tao Hou,Xiaoyan Chen,Yan Guo,Jun Hu

doi:10.1590/fst.66121

Abstract

Salted duck egg white was desalted and hydrolyzed to produce angiotensin I-converting enzyme (ACE) inhibitory peptides. Single factor test and response surface design were performed to determine the best hydrolysis conditions: enzyme dosage 11875.99 U/g, substrate concentration 33.04 g/L and hydrolysis time 4 h. The fraction V (MW < 1 kDa), which exhibited the strongest ACE inhibitory activity, was characterized by HPLC-ESI-MS/MS. Eighty-three peptides were identified, and among them Ile-Leu-Lys-Pro, Ile-Asn-Ser-Trp, Ile-Arg and His-Pro-Ala were synthesized for further research. Ile-Leu-Lys-Pro exhibited the highest ACE inhibitory activity (IC50: 0.355 mM). The molecular docking studies revealed that nine amino acids contributed to stabilize the docking complex. The ACE inhibition of Ile-Leu-Lys-Pro and Ile-Asn-Ser-Trp were mainly attributed to Ile in N-terminal. The residues Glu362 and Ala332 were the important binding sites in molecular docking. This research expands the understanding of ACE inhibitory peptides from duck egg white as well as highlights an opportunity for recycling an otherwise discarded byproduct.

Highlights

Angiotensin converting enzyme (ACE) has a significant impact on the regulation of blood pressure and it promotes the transformation of angiotensin I to angiotensin II by inactivating the potent vasodilator bradykinin in the circulatory or endocrine of human renin-angiotensin system (Jimsheena & Gowda, 2010)
Porcine skin gelatin was hydrolyzed with a targeted enzymatic approach (Aspergillus niger prolyl endoproteinase) to produce hydrolysate with potent angiotensin I-converting enzyme (ACE) inhibitory activity after 4-h hydrolysis and the sequence was identified as Met-Gly-Pro (O’Keeffe et al, 2017)
It was reported that proteases in enzymatic hydrolysis resourced from plant, animals and microorganism might have high ACE inhibitory activity relatively (Forghani et al, 2016; Pandey et al, 2018)

Summary

Introduction

Angiotensin converting enzyme (ACE) has a significant impact on the regulation of blood pressure and it promotes the transformation of angiotensin I to angiotensin II by inactivating the potent vasodilator bradykinin in the circulatory or endocrine of human renin-angiotensin system (Jimsheena & Gowda, 2010). ACE is identified as a potential target for synthetic pharmaceuticals, which inhibited ACE activity to reduce blood pressure. Peptides derived from natural food with high ACE inhibitory activity were preferred for their safety (Ngo et al, 2016). It has been reported that bovine collagen was a potential precursor of ACE inhibitory peptides based on in silico and in vitro protein digestions and two promising in silico peptides (Tyr-Trp and Leu-Arg-Tyr) were confirmed as novel ACE inhibitors (Fu et al, 2016). Porcine skin gelatin was hydrolyzed with a targeted enzymatic approach (Aspergillus niger prolyl endoproteinase) to produce hydrolysate with potent ACE inhibitory activity after 4-h hydrolysis and the sequence was identified as Met-Gly-Pro (O’Keeffe et al, 2017). Leu-Ser-Trp was previously identified from thermolysin-digested soy protein hydrolysate as a potent ACE-inhibitory peptide (Lin et al, 2017). Sweet sorghum grain protein hydrolysate was fractionated to four fractions (>10, 5-10, 1-5 and

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Conclusion