Enzymes of the Renin-Angiotensin System and their Inhibitors

Ondetti, Miguel A.; Cushman, David

doi:10.1146/annurev.bi.51.070182.001435

Cited by 448 publications

(212 citation statements)

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“…Structure-activity relationships among different peptide inhibitors of ACE indicate that binding to ACE is strongly influenced by the C-terminal tripeptide sequence of the substrate. Ondetti and Cushman (1982) proposed a binding model for interactions between the substrate and active site of ACE. The C-terminal tripeptide residues may interact with the subsites S 1 , S 1 ', and S 2 ' at the active site of ACE.…”

Section: Resultsmentioning

confidence: 99%

“…The relationships between the structure and activity level of various ACE inhibitory peptides indicate that binding to ACE is strongly influenced by the C-terminal tripeptide sequence of the substrate. The C-terminal tripeptide residues may interact with subsites at the active site of ACE (Ondetti and Cushman, 1982). ACE prefers to have substrates or competitive inhibitors that contain hydrophobic amino acid residues such as proline, phenylalanine, and tyrosine at three positions from the C-terminal (Cheung et al, 1980).…”

Section: Introductionmentioning

confidence: 99%

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Structure and Activity of Angiotensin I Converting Enzyme Inhibitory Peptides Derived from Alaskan Pollack Skin

Byun¹,

Kim²

2002

BMB Reports

110

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Angiotensin I that converts the enzyme (ACE) inhibitory peptide, Gly-Pro-Leu, previously purified and identified from the Alaskan pollack skin gelatin hydrolysate, were synthesized. In addition, the peptides Gly-Leu-Pro, LeuGly-Pro, Leu-Pro-Gly, Pro-Gly-Leu, Pro-Leu-Gly, GlyPro, and Pro-Leu, which consisted of glycine, proline, and leucine, were synthesized by the solid-phase method. The IC 50 values of each tripeptide − namely Leu-Gly-Pro, GlyLeu-Pro, Gly-Pro-Leu, Pro-Leu-Gly, Leu-Pro-Gly, and Pro-Gly-Leu − were 0.72, 1.62, 2.65, 4.74, 5.73, and 13.93 µM, respectively. The ACE inhibitory activity of these tripeptides was higher than that of dipeptides, such as GlyPro and Pro-Leu with IC 50 values of 252.6 and 337.3 µM, respectively. Among the tripeptides, Leu-Gly-Pro and GlyLeu-Pro had higher inhibitory activity than Gly-Pro-Leu that was isolated from the Alaskan pollack skin gelatin hydrolysate. Among the different types of tripeptides that were examined, the highest ACE inhibitory activity was observed for Leu-Gly-Pro. It had the leucine residue at the N-terminal and proline residue at the C-terminal.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structure and Activity of Angiotensin I Converting Enzyme Inhibitory Peptides Derived from Alaskan Pollack Skin

Byun¹,

Kim²

2002

BMB Reports

110

View full text Add to dashboard Cite

show abstract

“…Structure-activity relationships among different peptide inhibitors of ACE indicate that binding to ACE is strongly influenced by the C -terminal tripeptide sequence of the substrate. Dndetti & Cushman (1982) proposed a binding model for interactions between the substrate and active site of ACE. The C -terminal tripeptide residues may interact with the subsites S1, S1' , and S2' at the active site of ACE.…”

Section: Amino Acid Compositionmentioning

confidence: 99%

ACE-I inhibitory properties of hydrolysates from germinated and ungerminated Phaseolus lunatus proteins

Magaña¹,

Campos²,

Dávila-Ortíz³

et al. 2015

Food Sci. Technol (Campinas)

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Phaseolus lunatus protein concentrates and the proteases Alcalase (R) and Pepsin-Pancreatin were used for the production of protein hydrolysates that inhibit angiotensin-I converting enzyme (ACE). Protein concentrate obtained from germinated and ungerminated seeds flour was hydrolyzed with Alcalase (R) at enzyme/substrate ratio (E/S) 1/10 and during 0.5 and 2.0 h, respectively. Dn the other hand, protein concentrate obtained from ungerminated (E/S: 1/10) and germinated (E/S: 1/50) seeds flour was sequentially hydrolyzed with Pepsin-Pancreatin during 1.0 and 3.0 h, respectively. Peptide fractions with ACE inhibitory activity in a range of 0.9 to 3.8 µg/mL were obtained by G-50 gel filtration chromatography and high-performance liquid chromatography C18 reverse phase chromatography. The observed amino acid composition suggests a substantial contribution of hydrophobic residues to the peptides' inhibitory potency, which potentially acts via blocking of angiotensin II production. These results show that P. lunatus seed proteins are a potential source of ACE inhibitory peptides when hydrolyzed with Alcalase (R) and Pepsin-Pancreatin.Keywords: P. lunatus; hydrolysates; peptides; ACE inhibitory activity.Practical Application: Legume proteins can enzymatically produce bioactive specific peptides for use in functional foods.

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“…Ингибиторы АПФ были впервые открыты более 40 лет назад в яде змеи Bothrops jararaca как вещества, обладающие способностью потенциировать действие Бк [78]. Первым синтетическим ингибитором, вошедшим в клиническую практику, стал каптоприл [79]. С тех пор было синтезировано большое количество высокоэффективных иАПФ, которые наряду с каптоприлом широко применяются в клинике [80].…”

Section: активация рецепторов кининов ингибиторами апфunclassified

Ace inhibitors - activators of kinin receptors

Kugaevskaya

Elisseeva

2011

BIOMED KHIM

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Angiotensin converting enzyme (ACE) inhibitors are widely used for treatment of cardiovascular diseases. The effects of ACE inhibitors on the human bradykinin receptors were investigated. The mode of action of ACE inhibitors is considered. There is evidence that ACE inhibitors exert effects on the vascular system that cannot be attributed simply to the inhibition of ACE activity and accumulation of locally produced bradykinin. ACE inhibitors augment bradykinin effects on receptors indirectly by inducing cross-talk between ACE and the B2 receptor when enzyme and receptor molecules are sterically close, possibly forming a heterodimer. ACE inhibitors activate B1 receptors directly and independently of ACE via the zink-binding consensus sequence HEXXH, which is present in B1, but not in B2 receptor. Particular structure of B2 and B1 are represented, as well as receptor amino acids coupled with the G-proteins. Activation of kinin receptors by ACE inhibitors leads to clinically beneficial effects of ACE inhibitors.

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Enzymes of the Renin-Angiotensin System and their Inhibitors

Cited by 448 publications

References 1 publication

Structure and Activity of Angiotensin I Converting Enzyme Inhibitory Peptides Derived from Alaskan Pollack Skin

Structure and Activity of Angiotensin I Converting Enzyme Inhibitory Peptides Derived from Alaskan Pollack Skin

ACE-I inhibitory properties of hydrolysates from germinated and ungerminated Phaseolus lunatus proteins

Ace inhibitors - activators of kinin receptors

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