Enzima conversora de angiotensina no líquido pericárdico: estudo comparativo com a atividade sérica

Gomes, Roseli Aparecida da Silva; Teodoro, Lívia das Graças Vieito Lombardi; Lopes, Isabel Cristina Rezende; Bersanetti, Patrícia Alessandra; Carmona, Adriana Karaoglanovic; Hial, Valdemar

doi:10.1590/s0066-782x2008001500006

Cited by 8 publications

(2 citation statements)

References 34 publications

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“…The ACE presents two homologous domains (N and C) with a catalytic site present in each one, which may be differentially active in the several isoforms of the enzyme. The description of the active sites and their role in the hydrolysis of various physiological substrates is of great importance, so that subtle variations of specific amino acid residues in their substrates influence the catalytic specificity of the C-and Ndomain [2,5,6]. Araújo (2000) found that peptides with hydrophobic residues at the P1 position and peptides with bulky groups in the P2 position are preferably hydrolyzed in the C-domain of ACE, such as occurs in angiotensin I [7,8].…”

Section: Introductionmentioning

confidence: 99%

Structure-function studies of BPP-BrachyNH2 and synthetic analogues thereof with Angiotensin I-Converting Enzyme

Arcanjo

Vasconcelos

Nascimento

et al. 2017

European Journal of Medicinal Chemistry

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The vasoactive proline-rich oligopeptide termed BPP-BrachyNH (H-WPPPKVSP-NH) induces in vitro inhibitory activity of angiotensin I-converting enzyme (ACE) in rat blood serum. In the present study, the removal of N-terminal tryptophan or C-terminal proline from BPP-BrachyNH was investigated in order to predict which structural components are important or required for interaction with ACE. Furthermore, the toxicological profile was assessed by in silico prediction and in vitro MTT assay. Two BPP-BrachyNH analogues (des-Trp-BPP-BrachyNH and des-Pro-BPP-BrachyNH) were synthesized, and in vitro and in silico ACE inhibitory activity and toxicological profile were assessed. The des-Trp-BPP-BrachyNH and des-Pro-BPP-BrachyNH were respectively 3.2- and 29.5-fold less active than the BPP-BrachyNH-induced ACE inhibitory activity. Molecular Dynamic and Molecular Mechanics Poisson-Boltzmann Surface Area simulations (MM-PBSA) demonstrated that the ACE/BBP-BrachyNH complex showed lower binding and van der Wall energies than the ACE/des-Pro-BPP-BrachyNH complex, therefore having better stability. The removal of the N-terminal tryptophan increased the in silico predicted toxicological effects and cytotoxicity when compared with BPP-BrachyNH or des-Pro-BPP-BrachyNH. Otherwise, des-Pro-BPP-BrachyNH was 190-fold less cytotoxic than BPP-BrachyNH. Thus, the removal of C-terminal proline residue was able to markedly decrease both the BPP-BrachyNH-induced ACE inhibitory and cytotoxic effects assessed by in vitro and in silico approaches. In conclusion, the aminoacid sequence of BPP-BrachyNH is essential for its ACE inhibitory activity and associated with an acceptable toxicological profile. The perspective of the interactions of BPP-BrachyNH with ACE found in the present study can be used for development of drugs with differential therapeutic profile than current ACE inhibitors.

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Section: Introductionmentioning

confidence: 99%

Structure-function studies of BPP-BrachyNH2 and synthetic analogues thereof with Angiotensin I-Converting Enzyme

Arcanjo

Vasconcelos

Nascimento

et al. 2017

European Journal of Medicinal Chemistry

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“…As ACE is an important therapeutic target, especially to cardiovascular diseases, there are many studies about ACE inhibitors; however, molecular studies on its natural substrates are not widespread. Some experimental researches has already been published by our group,12 but few in silico studies have been performed and usually with smaller substrates such as Hippuryl–Histidine–Leucine 13…”

Section: Introductionmentioning

confidence: 99%

Molecular modeling of bioactive neuropeptides: Substrates of angiotensin I‐converting enzyme

Santos

Sonoda

Gomes

et al. 2012

Int J of Quantum Chemistry

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Angiotensin I (Ang-I)-converting enzyme (ACE) is a chloridedependent zinc metallopeptidase that is important in the regulation of cardiovascular functions. In addition to Ang-I and bradykinin, ACE is able to cleave several other peptides, such as neurotensin (NT), substance P, and Angiotensin-(1-7) (Ang-1-7). We have investigated by computational methods the structural and dynamical similarities among these peptides that could be responsible to their molecular recognition by ACE. Conformational and clustering analyses, semiempirical, and density functional theory calculations were performed; in addition, molecular dynamics (MD) simulations of Ang-1-7 both in pure water and in saline conditions were undertaken. Backbones folding pattern between the conformers of each peptide was very similar, mainly sustained by noncovalent interactions, denoting high conservation of the cleavage site. Also, cleavage site showed high folding similarity between the three different substrates and could mean a structural pattern. Highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital showed no pattern between the substrates; however, HOMO is located at the cleavage site. MD studies showed that Ang-(1-7) has faster relaxation in saline system and less content of intramolecular hydrogen bonds, which could explain the higher cleavage activity of this peptide by ACE in such conditions.

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Apelin/APJ system: a promising therapy target for hypertension

Chen

2014

Mol Biol Rep

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Apelin is a recently described endogenous peptide and its receptor APJ, is a member of the G protein-coupled receptors family. Apelin and APJ are widely distributed in central and peripheral tissues exert important biological effects on cardiovascular system. Recent studies have suggested that apelin/APJ system involves in decreasing the blood pressure and have a close relationship with hypertension, presumably, pathophysiology of hypertension as well. Such as, apelin/APJ system may be concerned in hyperfunction of the sympathetic nervous system, renin-angiotensin-aldosterone system, endothelial injury, excessive endothelin, sodium retention, vascular remodeling, insulin resistance elicit hypertension, as well as in hypertension-induced organ damaged. Meanwhile, on the ground of the variation of apelin level in hypertension therapeutic process and combining with the recently researches on APJ agonist and antagonist, we could infer that apelin/APJ system would be a promising therapeutic target for hypertension and other cardiovascular disease in the future. However, the role of apelin on these pathogenic conditions was not consistent, consequently, the contradictory role of apelin on these pathogenesis of hypertension would be discussed in this article.

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Enzima conversora de angiotensina no líquido pericárdico: estudo comparativo com a atividade sérica

Abstract: SummaryBackground: The characterization of an angiotensin-converting enzyme (ACE) in human pericardial fluid is relevant, considering its role in the angiotensin II release and thus, the role of the pericardium in cardiovascular homeostasis.

Cited by 8 publications

References 34 publications

Structure-function studies of BPP-BrachyNH2 and synthetic analogues thereof with Angiotensin I-Converting Enzyme

Structure-function studies of BPP-BrachyNH2 and synthetic analogues thereof with Angiotensin I-Converting Enzyme

Molecular modeling of bioactive neuropeptides: Substrates of angiotensin I‐converting enzyme

Apelin/APJ system: a promising therapy target for hypertension

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