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

Aino Siltari,1 Riikka Viitanen,2 Sampo Kukkurainen,2 Heikki Vapaatalo,1 Jarkko Valjakka2 1Institute of Biomedicine, Pharmacology, University of Helsinki, Finland; 2BioMediTech, Institute of Biomedical Technology, University of Tampere, Finland Background: The milk casein-derived bioactive tripepti...

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Autores principales:	Siltari A, Viitanen R, Kukkurainen S, Vapaatalo H, Valjakka J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/84c9f1c9de43465499f369c5461dff0e
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spelling	oai:doaj.org-article:84c9f1c9de43465499f369c5461dff0e2021-12-02T06:13:10ZDoes the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ACE-1 enzyme inhibition?1177-5475https://doaj.org/article/84c9f1c9de43465499f369c5461dff0e2014-02-01T00:00:00Zhttp://www.dovepress.com/does-the-cistrans-configuration-of-peptide-bonds-in-bioactive-tripepti-a15755https://doaj.org/toc/1177-5475 Aino Siltari,1 Riikka Viitanen,2 Sampo Kukkurainen,2 Heikki Vapaatalo,1 Jarkko Valjakka2 1Institute of Biomedicine, Pharmacology, University of Helsinki, Finland; 2BioMediTech, Institute of Biomedical Technology, University of Tampere, Finland 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. Keywords: ACE inhibition, Autodock modeling, Ile-Pro-Pro, Val-Pro-Pro, vascular functionSiltari AViitanen RKukkurainen SVapaatalo HValjakka JDove Medical PressarticleMedicine (General)R5-920ENBiologics: Targets & Therapy, Vol 2014, Iss default, Pp 59-65 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Siltari A Viitanen R Kukkurainen S Vapaatalo H Valjakka J Does the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ACE-1 enzyme inhibition?
description	Aino Siltari,1 Riikka Viitanen,2 Sampo Kukkurainen,2 Heikki Vapaatalo,1 Jarkko Valjakka2 1Institute of Biomedicine, Pharmacology, University of Helsinki, Finland; 2BioMediTech, Institute of Biomedical Technology, University of Tampere, Finland 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. Keywords: ACE inhibition, Autodock modeling, Ile-Pro-Pro, Val-Pro-Pro, vascular function
format	article
author	Siltari A Viitanen R Kukkurainen S Vapaatalo H Valjakka J
author_facet	Siltari A Viitanen R Kukkurainen S Vapaatalo H Valjakka J
author_sort	Siltari A
title	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_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_sort	does the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ace-1 enzyme inhibition?
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/84c9f1c9de43465499f369c5461dff0e
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Does the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ACE-1 enzyme inhibition?

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