title: Does the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ACE-1 enzyme inhibition?
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Institute of Biomedicine, Pharmacology, University of Helsinki, Finland.
authors.forename: Aino
authors.initials: A
authors.lastname: Siltari
authors.affiliation: BioMediTech, Institute of Biomedical Technology, University of Tampere, Finland.
authors.forename: Riikka
authors.initials: R
authors.lastname: Viitanen
authors.affiliation: BioMediTech, Institute of Biomedical Technology, University of Tampere, Finland.
authors.forename: Sampo
authors.initials: S
authors.lastname: Kukkurainen
authors.affiliation: Institute of Biomedicine, Pharmacology, University of Helsinki, Finland.
authors.forename: Heikki
authors.initials: H
authors.lastname: Vapaatalo
authors.affiliation: BioMediTech, Institute of Biomedical Technology, University of Tampere, Finland.
authors.forename: Jarkko
authors.initials: J
authors.lastname: Valjakka
keywords: ACE inhibition; Autodock modeling; Ile-Pro-Pro; Val-Pro-Pro; vascular function