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Does the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ACE-1 enzyme inhibition?

BACKGROUND: The milk casein-derived bioactive tripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) have been shown to prevent development of hypertension in animal models and to lower blood pressure in moderately hypertensive subjects in most but not all clinical trials. Inh...

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Autores principales: Siltari, Aino, Viitanen, Riikka, Kukkurainen, Sampo, Vapaatalo, Heikki, Valjakka, Jarkko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930482/
https://www.ncbi.nlm.nih.gov/pubmed/24596454
http://dx.doi.org/10.2147/BTT.S54056
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author Siltari, Aino
Viitanen, Riikka
Kukkurainen, Sampo
Vapaatalo, Heikki
Valjakka, Jarkko
author_facet Siltari, Aino
Viitanen, Riikka
Kukkurainen, Sampo
Vapaatalo, Heikki
Valjakka, Jarkko
author_sort Siltari, Aino
collection PubMed
description BACKGROUND: The milk casein-derived bioactive tripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) have been shown to prevent development of hypertension in animal models and to lower blood pressure in moderately hypertensive subjects in most but not all clinical trials. Inhibition of angiotensin-converting enzyme 1 (ACE-1) has been suggested as the explanation for these antihypertensive and beneficial vascular effects. Previously, human umbilical vein endothelial cells (HUVEC) have not been used to test ACE-1 inhibiting properties of casein derived tripeptides in vasculature. PURPOSE: We focused on the cis/trans configurations of the peptide bonds in proline-containing tripeptides in order to discover whether the different structural properties of these peptides influence their activity in ACE-1 inhibition. We hypothesized that the configuration of proline-containing peptides plays a significant role in enzyme inhibition. METHODS: AutoDock 4.2 docking software was used to predict suitable peptide bond configurations of the tripeptides. Besides modeling studies, we completed ACE-1 activity measurements in vitro using HUVEC cultures. RESULTS: In HUVEC cells, both IPP and VPP inhibited ACE-1. Based on molecular docking studies, we propose that in ACE-1 inhibition IPP and VPP share a similar cis configuration between the first aliphatic (isoleucine or valine) and the second (proline) amino acid residues and more different configurations between two proline residues. In vivo experiments are needed to validate the significance of the present findings.
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spelling pubmed-39304822014-03-04 Does the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ACE-1 enzyme inhibition? Siltari, Aino Viitanen, Riikka Kukkurainen, Sampo Vapaatalo, Heikki Valjakka, Jarkko Biologics Hypothesis BACKGROUND: The milk casein-derived bioactive tripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) have been shown to prevent development of hypertension in animal models and to lower blood pressure in moderately hypertensive subjects in most but not all clinical trials. Inhibition of angiotensin-converting enzyme 1 (ACE-1) has been suggested as the explanation for these antihypertensive and beneficial vascular effects. Previously, human umbilical vein endothelial cells (HUVEC) have not been used to test ACE-1 inhibiting properties of casein derived tripeptides in vasculature. PURPOSE: We focused on the cis/trans configurations of the peptide bonds in proline-containing tripeptides in order to discover whether the different structural properties of these peptides influence their activity in ACE-1 inhibition. We hypothesized that the configuration of proline-containing peptides plays a significant role in enzyme inhibition. METHODS: AutoDock 4.2 docking software was used to predict suitable peptide bond configurations of the tripeptides. Besides modeling studies, we completed ACE-1 activity measurements in vitro using HUVEC cultures. RESULTS: In HUVEC cells, both IPP and VPP inhibited ACE-1. Based on molecular docking studies, we propose that in ACE-1 inhibition IPP and VPP share a similar cis configuration between the first aliphatic (isoleucine or valine) and the second (proline) amino acid residues and more different configurations between two proline residues. In vivo experiments are needed to validate the significance of the present findings. Dove Medical Press 2014-02-11 /pmc/articles/PMC3930482/ /pubmed/24596454 http://dx.doi.org/10.2147/BTT.S54056 Text en © 2014 Siltari et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Hypothesis
Siltari, Aino
Viitanen, Riikka
Kukkurainen, Sampo
Vapaatalo, Heikki
Valjakka, Jarkko
Does the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ACE-1 enzyme inhibition?
title Does the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ACE-1 enzyme inhibition?
title_full Does the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ACE-1 enzyme inhibition?
title_fullStr Does the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ACE-1 enzyme inhibition?
title_full_unstemmed Does the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ACE-1 enzyme inhibition?
title_short Does the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ACE-1 enzyme inhibition?
title_sort does the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ace-1 enzyme inhibition?
topic Hypothesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930482/
https://www.ncbi.nlm.nih.gov/pubmed/24596454
http://dx.doi.org/10.2147/BTT.S54056
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