Active-site directed peptide l-Phe-d-His-l-Leu inhibits angiotensin converting enzyme activity and dexamethasone-induced hypertension in rats

Savitha, Mysuru Natarajan; Siddesha, Jalahalli M.; Suvilesh, Kanve Nagaraj; Manjunath, Yariswamy; Vivek, H. K.; D'Souza, Cletus J. M.; Muddegowda, Umashankar; Vishwanath, Bannikuppe S.

doi:10.1016/j.peptides.2018.11.002

Cited by 14 publications

(13 citation statements)

References 43 publications

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“…Authors performed docking experiments in nACE and cACE, suggesting a preference for the N domain. In other work, Savitha et al [54] reported the ACE-inhibitory potential of the tripeptide L-Phe-D-His-L-Leu in vitro and its antihypertensive effect in rat model of dexamethasone-induced hypertension. They performed docking experiments to study the mode of action of the studied peptide.…”

Section: Molecular Modeling Applied To the Study Of Ace Inhibitors Inmentioning

confidence: 96%

Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors

Caballero

2020

Molecules

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The angiotensin-converting enzyme (ACE) is a two-domain dipeptidylcarboxypeptidase, which has a direct involvement in the control of blood pressure by performing the hydrolysis of angiotensin I to produce angiotensin II. At the same time, ACE hydrolyzes other substrates such as the vasodilator peptide bradykinin and the anti-inflammatory peptide N-acetyl-SDKP. In this sense, ACE inhibitors are bioactive substances with potential use as medicinal products for treatment or prevention of hypertension, heart failures, myocardial infarction, and other important diseases. This review examined the most recent literature reporting ACE inhibitors with the help of molecular modeling. The examples exposed here demonstrate that molecular modeling methods, including docking, molecular dynamics (MD) simulations, quantitative structure-activity relationship (QSAR), etc, are essential for a complete structural picture of the mode of action of ACE inhibitors, where molecular docking has a key role. Examples show that too many works identified ACE inhibitory activities of natural peptides and peptides obtained from hydrolysates. In addition, other works report non-peptide compounds extracted from natural sources and synthetic compounds. In all these cases, molecular docking was used to provide explanation of the chemical interactions between inhibitors and the ACE binding sites. For docking applications, most of the examples exposed here do not consider that: (i) ACE has two domains (nACE and cACE) with available X-ray structures, which are relevant for the design of selective inhibitors, and (ii) nACE and cACE binding sites have large dimensions, which leads to non-reliable solutions during docking calculations. In support of the solution of these problems, the structural information found in Protein Data Bank (PDB) was used to perform an interaction fingerprints (IFPs) analysis applied on both nACE and cACE domains. This analysis provides plots that identify the chemical interactions between ligands and both ACE binding sites, which can be used to guide docking experiments in the search of selective natural components or novel drugs. In addition, the use of hydrogen bond constraints in the S2 and S2′ subsites of nACE and cACE are suggested to guarantee that docking solutions are reliable.

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Section: Molecular Modeling Applied To the Study Of Ace Inhibitors Inmentioning

confidence: 96%

Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors

Caballero

2020

Molecules

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“…Peptide sequences are annotated in the BIOPEP-UWM database of bioactive peptides using a standard one-letter code describing 20 protein amino acids and their d -enantiomers (a recently added option). A peptide with the FhL sequence ( l -Phe- d -His- l -Leu) [19] (BIOPEP-UWM ID 9475) may serve as an example of the peptide containing D-amino acid residue. The database offers an opportunity to annotate C-terminal amidation using the “~” symbol [8].…”

Section: Peptide Informationmentioning

confidence: 99%

BIOPEP-UWM Database of Bioactive Peptides: Current Opportunities

Minkiewicz

Iwaniak

Darewicz

2019

IJMS

585

397

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The BIOPEP-UWM™ database of bioactive peptides (formerly BIOPEP) has recently become a popular tool in the research on bioactive peptides, especially on these derived from foods and being constituents of diets that prevent development of chronic diseases. The database is continuously updated and modified. The addition of new peptides and the introduction of new information about the existing ones (e.g., chemical codes and references to other databases) is in progress. New opportunities include the possibility of annotating peptides containing D-enantiomers of amino acids, batch processing option, converting amino acid sequences into SMILES code, new quantitative parameters characterizing the presence of bioactive fragments in protein sequences, and finding proteinases that release particular peptides.

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“…Molecular docking results were validated by using a standard inhibitor Lisinopril, which forms hydrogen bond with His513, Glu384, Tyr523, Try520, Lys511, Arg523, Ala356, Glu162 and salt bridge with Zinc and Glu162 ( Figure 11 a). These interactions with amino acids are very important during catalysis [ 66 , 67 ]. The three-dimensional view of the standard Lisinopril shows that the Lisinopril deeply binds at the active site ( Figure 11 b).…”

Section: Resultsmentioning

confidence: 99%

Design and synthesis of coumarin-triazole hybrids: biocompatible anti-diabetic agents, in silico molecular docking and ADME screening

Basappa

Vivek²,

Kumara

et al. 2020

Heliyon

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The current study demonstrates the synthesis of coumarin-triazole hybrids 8 (a-e) in four steps starting from substituted salicylaldehyde 1 (a-e), and diethyl malonate 2. The spectroscopic studies provide the structure proofs of the new compounds, and the molecular structure of an intermediate 3a by crystallographic studies. The crystal structure analysis revealed the C-H...O, C-H... π, CO ...π and π...π molecular interactions. Further, the intermolecular interactions were quantified using Hirshfeld surface analysis and the DFT method B3LYP functional with 6-311þþ G (d,p) basis set was employed to optimize the molecular geometry. The synthesized new coumarintriazole hybrids, 8 (a-e) were screened for their α-amylase inhibitory potentials, and the results suggest that amongst the series, compounds 8c, and 8e show the promising inhibition of the enzyme, and might act as lead molecules for anti-diabetic activities. To understand the mode of action in silico molecular docking and ADME screening were performed.

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Active-site directed peptide l-Phe-d-His-l-Leu inhibits angiotensin converting enzyme activity and dexamethasone-induced hypertension in rats

Cited by 14 publications

References 43 publications

Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors

Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors

BIOPEP-UWM Database of Bioactive Peptides: Current Opportunities

Design and synthesis of coumarin-triazole hybrids: biocompatible anti-diabetic agents, in silico molecular docking and ADME screening

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