Angiotensin I-converting enzyme inhibitory peptides from Sipuncula (Phascolosoma esculenta): Purification, identification, molecular docking and antihypertensive effects on spontaneously hypertensive rats

Guo, Mingrong; Chen, Xujun; Wu, Yanling; Zhang, Lujia; Huang, Weixue; Yuan, Ying; Fang, Ming; Xie, Junxia; Wei, Dongzhi

doi:10.1016/j.procbio.2017.08.009

Cited by 38 publications

(31 citation statements)

References 37 publications

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“…In the previous study, YASGR and GNGSGYVSR were demonstrated to significantly reduce blood pressure of SHRs. Moreover, YASGR was docked into the active pockets of ACE with the residues Ala354 and His353, and GNGSGYVSR‐ACE complex were stabilized by binding with the residues Glu384 and Tyr523 (Guo et al, ). Simultaneously, VL‐9 (VLESFPPK) interaction with S 2 pocket (His513, His353, Glu281) and S 1 ’ pocket (Glu162) of ACE, moreover, LL‐9 (LPESVHLDK) (Mirzaei, Mirdamadi, Ehsani, & Aminlari, ) could be docked into S 2 (Gln281, Lys511, Tyr520) of ACE.…”

Section: Resultsmentioning

confidence: 99%

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Novel ACE inhibitors derived from soybean proteins using in silico and in vitro studies

Zhao

Xue

et al. 2019

J Food Biochem

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The widespread application of soybean‐derived peptides is currently limited due to the challenges in the identification of peptides. In the present work, in silico and in vitro analysis were applied to identify ACE inhibitory tri‐peptides from soybean protein. The soybean protein was cleaved by PeptideCutter. Then, unknown tri‐peptides were selected to solubility estimation and ADME prediction. Subsequently, Discovery Studio was applied to evaluate the interaction mechanism between ACE and tri‐peptides. Finally, in vitro activity of theoretical ACE inhibitory tri‐peptides was verified by RP‐HPLC method. As a result, DMG was selected as a potent ACE inhibitory peptide. Cell experiment showed that DMG had no cytotoxic effects on HEK‐293 cells. And molecular docking results indicated that DMG contacted well with ACE’s active sites (Gln281, His353, Ala354, Glu384, Lys511, His513, and Tyr520). Furthermore, DMG could exert potent activity against ACE, with IC50 value of 3.95 ± 0.11 mM. Practical applications Present research showed soybean is a potential protein resource to obtain ACE inhibitory peptides. Simultaneously, virtual screening method is a feasible way to substitute for classical method in emerging nutritional fields. What's more, present study provides a theoretical basis for industrial research on foodstuff for ACE inhibitory peptides without side effects.

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Section: Resultsmentioning

confidence: 99%

“…The pose of each ligand was selected based on the interaction energy (Duan et al, ). DS was used to distinguish salt bridge, conventional hydrogen bond, carbon hydrogen bond, pi‐alkyl, van de Waals, alkyl, and metal‐acceptor bond at the ACE active sites (Guo et al, ).…”

Section: Methodsmentioning

confidence: 99%

Novel ACE inhibitors derived from soybean proteins using in silico and in vitro studies

Zhao

Xue

et al. 2019

J Food Biochem

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“…FQIN [M(O)] CILR (IC50 = 9.64 ± 0.36 μM) and TGAPCR (IC50 = 23.94 ± 0.82 μM) were also screened from trypsin hydrolyzate of G. lemaneiformis , but the two peptides have lower IC50 values than the ACE inhibitory peptide reported above. The two peptides isolated from G. lemaneiformis showed higher activity than some reported C-terminal arginine ACE inhibitory peptides YIPIQYVLSR (IC50 = 132.5 μM), YASGR (IC50 = 184 μM) and GNGSGYVSR (IC50 = 29 μM) [ 32 , 33 ]. According to earlier studies, C-terminal arginine plays an important role in inhibiting the activity of ACE.…”

Section: Discussionmentioning

confidence: 91%

Antihypertensive Effects of Two Novel Angiotensin I-Converting Enzyme (ACE) Inhibitory Peptides from Gracilariopsis lemaneiformis (Rhodophyta) in Spontaneously Hypertensive Rats (SHRs)

et al. 2018

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A variety of biologically active products have been isolated from Gracilariopsis lemaneiformis. In the present study, two novel angiotensin-converting enzyme (ACE) inhibitory peptides, FQIN [M(O)] CILR, and TGAPCR, were screened and identified from G. lemaneiformis protein hydrolysates by LC-MS/MS. The IC50 values of FQIN [M(O)] CILR and TGAPCR were 9.64 ± 0.36 μM and 23.94 ± 0.82 μM, respectively. In the stability study, both peptides showed stabilities of pH, temperature, simulated gastrointestinal digestion, and ACE hydrolysis. The Lineweaver–Burk plot showed that the two peptides were noncompetitive inhibitors of ACE. Molecular docking simulated the intermolecular interactions of two peptides and ACE, and the two peptides formed hydrogen bonds with the active pockets of ACE. However, FQIN [M(O)] CILR was more closely linked to the active pockets of ACE, thereby exerting better ACE inhibition. Spontaneously hypertensive rats (SHRs) were studied with an oral dose of 10 mg/kg body weight. Both peptides reduced systolic blood pressure (SBP) and diastolic blood pressure (DBP) in SHRs, of which FQIN [M(O)] CILR was able to reduce the systolic blood pressure by 34 mmHg (SBP) (p < 0.05). Therefore, FQIN [M(O)] CILR was an excellent ACE inhibitory peptide.

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“…In order to avoid some challenges of the classical approach, such as having to apply cumbersome purification processes to isolate active peptides, the computer-based approach is considered a useful and effective method to identify novel peptides [35]. A number of docking algorithms are being used in multiple studies to predict potent ACE inhibitory peptides encrypted in food proteins [36][37][38][39][40][41][42], and more specifically in milk proteins [43,44], whereby attempts to understand the interactions between receptor and ligand are being attempted [45]. Molecular docking enables the investigation of the specific interactions between certain peptide sequences and specific binding site residues in ACE, which could help to provide a better prediction of bioactivity in vivo through a molecular understanding of the structure-function relationship.…”

Section: Introductionmentioning

confidence: 99%

Whey-Derived Peptides Interactions with ACE by Molecular Docking as a Potential Predictive Tool of Natural ACE Inhibitors

Chamata

Watson

Jauregi

2020

IJMS

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Several milk/whey derived peptides possess high in vitro angiotensin I-converting enzyme (ACE) inhibitory activity. However, in some cases, poor correlation between the in vitro ACE inhibitory activity and the in vivo antihypertensive activity has been observed. The aim of this study is to gain insight into the structure-activity relationship of peptide sequences present in whey/milk protein hydrolysates with high ACE inhibitory activity, which could lead to a better understanding and prediction of their in vivo antihypertensive activity. The potential interactions between peptides produced from whey proteins, previously reported as high ACE inhibitors such as IPP, LIVTQ, IIAE, LVYPFP, and human ACE were assessed using a molecular docking approach. The results show that peptides IIAE, LIVTQ, and LVYPFP formed strong H bonds with the amino acids Gln 259, His 331, and Thr 358 in the active site of the human ACE. Interestingly, the same residues were found to form strong hydrogen bonds with the ACE inhibitory drug Sampatrilat. Furthermore, peptides IIAE and LVYPFP interacted with the amino acid residues Gln 259 and His 331, respectively, also in common with other ACE-inhibitory drugs such as Captopril, Lisinopril and Elanapril. Additionally, IIAE interacted with the amino acid residue Asp 140 in common with Lisinopril, and LIVTQ interacted with Ala 332 in common with both Lisinopril and Elanapril. The peptides produced naturally from whey by enzymatic hydrolysis interacted with residues of the human ACE in common with potent ACE-inhibitory drugs which suggests that these natural peptides may be potent ACE inhibitors.

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Angiotensin I-converting enzyme inhibitory peptides from Sipuncula (Phascolosoma esculenta): Purification, identification, molecular docking and antihypertensive effects on spontaneously hypertensive rats

Cited by 38 publications

References 37 publications

Novel ACE inhibitors derived from soybean proteins using in silico and in vitro studies

Novel ACE inhibitors derived from soybean proteins using in silico and in vitro studies

Antihypertensive Effects of Two Novel Angiotensin I-Converting Enzyme (ACE) Inhibitory Peptides from Gracilariopsis lemaneiformis (Rhodophyta) in Spontaneously Hypertensive Rats (SHRs)

Whey-Derived Peptides Interactions with ACE by Molecular Docking as a Potential Predictive Tool of Natural ACE Inhibitors

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