Effect of varying chain length between P1 and P1′ position of tripeptidomimics on activity of angiotensin-converting enzyme inhibitors

Chaudhary, Snehlata; Vats, Ishwar Dutt; Chopra, Madhu; Biswas, Parbati; Pasha, Santosh

doi:10.1016/j.bmcl.2009.05.079

Cited by 31 publications

(18 citation statements)

References 20 publications

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“…The peptides and ACE residues are mainly linked through hydrogen bonds, hydrophobic interaction, and polar, Van der Waals, and electrostatic forces. It has been reported that hydrogen bond interactions play an irreplaceable role in stabilizing the structure of the complex as well as the ACE reaction [41,42]. Previous studies have indicated three main active site pockets in the ACE molecule.…”

Section: Resultsmentioning

confidence: 99%

Preparation and Identification of ACE Inhibitory Peptides from the Marine Macroalga Ulva intestinalis

Sun

et al. 2019

Marine Drugs

107

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Angiotensin I-converting enzyme (ACE) inhibitory peptides derived from seaweed represent a potential source of new antihypertensive. The aim of this study was to isolate and purify ACE inhibitory peptides (ACEIPs) from the protein hydrolysate of the marine macroalga Ulva intestinalis. U. intestinalis protein was hydrolyzed by five different proteases (trypsin, pepsin, papain, α-chymotrypsin, alcalase) to prepare peptides; compared with other hydrolysates, the trypsin hydrolysates exhibited the highest ACE inhibitory activity. The hydrolysis conditions were further optimized by response surface methodology (RSM), and the optimum conditions were as follows: pH 8.4, temperature 28.5 °C, enzyme/protein ratio (E/S) 4.0%, substrate concentration 15 mg/mL, and enzymolysis time 5.0 h. After fractionation and purification by ultrafiltration, gel exclusion chromatography and reverse-phase high-performance liquid chromatography, two novel purified ACE inhibitors with IC50 values of 219.35 μM (0.183 mg/mL) and 236.85 μM (0.179 mg/mL) were obtained. The molecular mass and amino acid sequence of the ACE inhibitory peptides were identified as Phe-Gly-Met-Pro-Leu-Asp-Arg (FGMPLDR; MW 834.41 Da) and Met-Glu-Leu-Val-Leu-Arg (MELVLR; MW 759.43 Da) by ultra-performance liquid chromatography-tandem mass spectrometry. A molecular docking study revealed that the ACE inhibitory activities of the peptides were mainly attributable to the hydrogen bond and Zn(II) interactions between the peptides and ACE. The results of this study provide a theoretical basis for the high-valued application of U. intestinalis and the development of food-derived ACE inhibitory peptides.

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Section: Resultsmentioning

confidence: 99%

Preparation and Identification of ACE Inhibitory Peptides from the Marine Macroalga Ulva intestinalis

Sun

et al. 2019

Marine Drugs

107

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“…. Among them, hydrogen bonding interactions play the most important role in stabilizing the docking complex and catalyzing enzyme reactions . Bi‐dimensional diagrams predict the interactions between substrates and individual MBSP amino acid residues.…”

Section: Resultsmentioning

confidence: 86%

“…Among them, hydrogen bonding interactions play the most important role in stabilizing the docking complex and catalyzing enzyme reactions. 20 Bi-dimensional diagrams predict the interactions between substrates and individual MBSP amino acid residues. Ultimately, the interaction score and the number of predicted hydrogen bonds and MBSP residues involved in interactions with the substrates were determined ( Table 3).…”

Section: Molecular Docking Analysismentioning

confidence: 99%

Altering the substrate specificity of a myofibril‐bound serine proteinase from Crucian carp by site‐directed mutagenesis

Mei

et al. 2018

J of Chemical Tech & Biotech

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BACKGROUND Myofibril‐bound serine proteinase (MBSP) comprises a class of trypsin‐type serine proteinases that can specifically cleave the carboxyl side of peptide bonds of arginine or lysine residues. To obtain higher specificity MBSPs, mutants were designed based on the substrate‐binding pocket and constructed through site‐directed mutagenesis. RESULTS The wild‐type (WT) and mutants were expressed in Pichia pastoris, and its enzymatic properties indicated that the mutants D170S, D170T, D170K and D170T/G203A were not biologically active. However, S171A specifically cleaved arginine residues and G203A preferably hydrolyzed lysine residues. The secondary structures of mutants were approximately similar to that of the WT according to the results of circular dichroism spectroscopy. Additionally, molecular docking showed that substrates were able to combine with S171A within the critical areas through hydrophobic interaction, hydrogen bonds and van der Waals electrostatic force. CONCLUSION The structural stability of MBSP was consistent using amino acid substitution. Due to the interaction pattern of substrates and mutant enzyme changes, only S171A was selective in cutting Arg residues, which illustrates how the catalytic triad and substrate‐binding pocket of MBSP plays an important role during enzymatic hydrolysis of substrates. © 2018 Society of Chemical Industry

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“…It is reported that active site Zn(II) atom of ACE binds to residues His383, His387, and Glu411 to format a tetrahedral geometry and usually plays a significant role for ACE activity [ 40 ]. It is also reported that hydrogen bonds interaction force plays the most important role in stabilizing the docking complex and enzyme catalytic reactions [ 41 ]. Accordingly, the dipeptide Cys-Cys established hydrogen bonds with the subsite pockets S1 (Ala354 and Tyr523), which was similar to most of ACE inhibitory peptides reported [ 7 , 9 , 14 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is conceivable that carboxylate docking, carboxy-terminal residue side chain interactions, and the coordination between carboxyl oxygen and Zn(II) and its distance are important in defining peptide ACE inhibitor potency [ 9 , 41 ]. In this study, the most potent ACE inhibitor among the dipeptides is Cys-Cys ( Table 2 ), which registered not only crucial coordination between carboxyl oxygen and Zn(II) but also interactions with ACE at Ala354 (O), Tyr523(OH), and His387(NE2).…”

Section: Discussionmentioning

confidence: 99%

Identification and Functional Mechanism of Novel Angiotensin I Converting Enzyme Inhibitory Dipeptides from Xerocomus badius Cultured in Shrimp Processing Waste Medium

Gao

Yan

et al. 2018

BioMed Research International

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ACE inhibitory dipeptides from Xerocomus badius fermented shrimp processing waste were isolated with ethanol, macroporous resin, chloroform, and Sephadex G-10 in sequence and identified by LC-MS/MS system coupled with electrospray ionization source. Molecular docking was performed for exploring the mechanism of their inhibitions. The results showed that the identified ACE inhibitory dipeptides were Cys-Cys and Cys-Arg with IC50 values of 4.37 ± 0.07 and 475.95 ± 0.11 μM, respectively. The difference between ACE inhibitor potency of Cys-Cys and Cys-Arg could be explained by results of molecular docking. Cys-Cys formed crucial coordination between carboxyl oxygen and Zn(II), hydrogen bonds with residues Ala354(O), Ala356(HN), and Tyr523(OH), and a bump with the residue His387(NE2) at the active site of ACE. There was no coordination, except for 5 hydrogen bonds (at residues His353, Ala354, Glu384, Glu403, and Arg522) and a bump (Glu411) between Cys-Arg and active site of ACE. These findings highlighted that Cys-Cys could be considered as a novel potent ACE inhibitor, and coordination between its carboxyl oxygen and Zn(II) played significant role in defining its ACE inhibitor potency.

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Effect of varying chain length between P1 and P1′ position of tripeptidomimics on activity of angiotensin-converting enzyme inhibitors

Cited by 31 publications

References 20 publications

Preparation and Identification of ACE Inhibitory Peptides from the Marine Macroalga Ulva intestinalis

Preparation and Identification of ACE Inhibitory Peptides from the Marine Macroalga Ulva intestinalis

Altering the substrate specificity of a myofibril‐bound serine proteinase from Crucian carp by site‐directed mutagenesis

Identification and Functional Mechanism of Novel Angiotensin I Converting Enzyme Inhibitory Dipeptides from Xerocomus badius Cultured in Shrimp Processing Waste Medium

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