Pharmacokinetic evaluation of lisinopril-tryptophan, a novel C-domain ACE inhibitor

Denti, Paolo; Sharp, Sarah-Kate; Kröger, Wendy L.; Schwager, S.L.U.; Mahajan, Aman; Njoroge, Mathew; Gibhard, Liezl; Smit, Ian; Chibale, Kelly; Wiesner, Lubbe; Sturrock, Edward D.; Davies, Neil

doi:10.1016/j.ejps.2014.01.012

Cited by 14 publications

(11 citation statements)

References 37 publications

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“…In order to verify the accuracy of the method，Bradykinin Potentiator B (BPPb) (150 nmol/L), angiotensin II (10 μmol/L), and lisinopril (150 nmol/L) were acted as positive controls (Denti et al., 2014; Masuyer et al., 2012; Sturrock et al., 2019). The ACE domain inhibitory activities of BPPb, angiotensin II and lisinopril were listed in Table 1, three kinds of inhibitors exhibit obviously higher inhibition on the C‐domain than on the N‐domain, which is consistent with the literature reports (Masuyer et al., 2012; Sturrock et al., 2019).…”

Section: Resultsmentioning

confidence: 99%

Study on the domain selective inhibition of angiotensin‐converting enzyme (ACE) by food‐derived tyrosine‐containing dipeptides

et al. 2021

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In this article, the selective inhibition of several tyrosine‐containing dipeptides on N and C domain of ACE (angiotensin‐converting enzyme) was studied, and the interaction mode of ACE and inhibitors was simulated by molecular docking. MTT assay was used to detect the effect of dipeptide on human umbilical vein endothelial cells (HUVEC). The results showed that the food‐derived dipeptides AY (Ala‐Tyr), LY (Leu‐Tyr), and IY (Ile‐Tyr) containing tyrosine at the C‐terminal were favorable structures for selective inhibition of ACE C‐domain. These dipeptides showed competitive and mixed inhibition patterns, while the dipeptides EY (Glu‐Tyr), RY (Arg‐Tyr), FY (Phe‐Tyr), and SY (Ser‐Tyr) showed noncompetitive inhibition. Food‐derived dipeptides containing tyrosine have no cytotoxicity on HUVEC cells, which provides a basis for the application of food‐derived tyrosine dipeptides as antihypertensive peptides. This study provides a theoretical basis for exploring the selective inhibition mechanism of ACE inhibitory peptides containing tyrosine residue. Practical applications Angiotensin‐converting enzyme (ACE) is a two‐domain dipeptidyl carboxypeptidase, which is a key enzyme to regulate blood pressure. ACE has two active sites, C‐ and N‐domain, which have high catalytic activity. Although the amino acid sequences of the two active sites have 60% similarity, there are some differences in structure and function. The action mechanism of ACE domain should be clarified, and the structure‐activity relationship between inhibitors and ACE domain has not been systematically studied. The aim of this study was to identify the selective inhibitory effect of food‐derived tyrosine dipeptides on the domain of ACE. This provides a new idea for finding new antihypertensive drugs with less side effects.

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Section: Resultsmentioning

confidence: 99%

Study on the domain selective inhibition of angiotensin‐converting enzyme (ACE) by food‐derived tyrosine‐containing dipeptides

et al. 2021

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“…28,29 This lower level of inhibition is also expected based on our previous in vitro and ex vivo results where LisW-S was found to have a lower potency than lisinopril. 16,17 It is important to note that in mice where higher dosages could be achieved, LisW-S administration via an osmotic pump resulted in similar reductions in blood pressure and Ang 1-8 levels in the kidney to that seen for lisinopril. 19 The low levels of Ang 1-8 observed in the kidneys of LisW-S-treated mice are intriguing as they may in part explain the even more substantial increase in Ang 1-10 for LisW-S relative to that seen with lisinopril.…”

Section: Discussionmentioning

confidence: 99%

“…This derivative, LisW-S, has been shown to be highly selective for the C-domain both in vitro and ex vivo. [16][17][18] Further to this, LisW-S has been found to be efficacious in lowering blood pressure in hypertensive mice that express active human renin in a similar fashion to that observed for lisinopril but without the increase in bradykinin levels induced by lisinopril. 19 The RAS is a complex proteolytic cascade of peptide products stemming from angiotensinogen involving multiple enzymes.…”

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confidence: 95%

Pharmacodynamic effects of C-domain-specific ACE inhibitors on the renin-angiotensin system in myocardial infarcted rats

Sharp

Poglitsch

Zilla

et al. 2015

J Renin Angiotensin Aldosterone Syst

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Introduction: The renin-angiotensin system (RAS) is a dynamic network that plays a critical role in blood pressure regulation and fluid and electrolyte homeostasis. Modulators of the RAS, such as angiotensin-converting enzyme (ACE) inhibitors, are widely used to treat hypertension, heart failure and myocardial infarction. Methods: The effect of ACE inhibitors (lisinopril and C-domain-selective LisW-S) on the constituent peptides of the RAS following myocardial infarction was examined in rats. Ten angiotensin peptides were analysed using a sensitive LC-MS/MS-based assay to examine both the circulating and equilibrium levels of these peptides. Results: Administration of lisinopril or LisW-S caused a significant decrease in Ang 1–8/Ang 1–10 ratios as determined by circulating and equilibrium peptide level analysis. Furthermore, Ang 1–7 levels were elevated by both ACE inhibitors, but only lisinopril decreased the Ang 1–5/Ang 1–7 ratio. This indicates LisW-S C-domain specificity as Ang 1–5 is generated by hydrolysis of Ang 1–7 by the N-domain. Further corroboration of LisW-S C-domain specificity is that only lisinopril increased the circulating levels of the N-domain ACE substrate Ac-SDKP. Conclusion: LisW-S is able to effectively block ACE in vivo by C-domain-selective inhibition. The LC-MS/MS-based assay allows the evaluation of the pharmacologic impact of RAS inhibitors in different pathophysiological conditions.

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“…It was reported that the structure of C-terminal tripeptide in the peptide chain is in favor of the combination between ACE-inhibitory peptides and ACE. [34,35] Moreover, aromatic amino acid content is 16.22% in F2.…”

Section: Amino Acid Analysismentioning

confidence: 99%

Changes of Composition and Angiotensin I-Converting Enzyme-Inhibitory Activity During Douchi Fermentation

Hui

Meng

Yin

et al. 2016

International Journal of Food Properties

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Douchi is a fermented soybean food, which is popular in China. Composition and ACE-inhibitory activity of Douchi fermented with Mucor wutungkiao were studied in this work. The results showed that the nutritional potency of protein, fat and soluble polysaccharide was improved in Douchi fermentation. The ACE-inhibitory activity of Douchi that ripening for two weeks showed the highest ACE-inhibitory activity. Then this sample was purified with Sephadex G-25 gel chromatography, and the amino acids and ACE-inhibitory activity of the purified fractions were Downloaded by [Rutgers University] at 11:17 15 August 2015A c c e p t e d M a n u s c r i p t 2 studied. The results suggested that hydrophobic amino acids were assumed to cause the main increase of the ACE-inhibitory activity in Douchi.

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Pharmacokinetic evaluation of lisinopril-tryptophan, a novel C-domain ACE inhibitor

Cited by 14 publications

References 37 publications

Study on the domain selective inhibition of angiotensin‐converting enzyme (ACE) by food‐derived tyrosine‐containing dipeptides

Study on the domain selective inhibition of angiotensin‐converting enzyme (ACE) by food‐derived tyrosine‐containing dipeptides

Pharmacodynamic effects of C-domain-specific ACE inhibitors on the renin-angiotensin system in myocardial infarcted rats

Changes of Composition and Angiotensin I-Converting Enzyme-Inhibitory Activity During Douchi Fermentation

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