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

Aino Siltari, Riikka Viitanen, Sampo Kukkurainen, Heikki Vapaatalo, Jarkko Valjakka

    Research output: Contribution to journalArticleScientificpeer-review

    16 Citations (Scopus)

    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. 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.

    Original languageEnglish
    Pages (from-to)59-65
    Number of pages7
    JournalBiologics: Targets and Therapy
    Volume8
    DOIs
    Publication statusPublished - 2014
    Publication typeA1 Journal article-refereed

    Keywords

    • ACE inhibition
    • AutoDock modeling
    • Autodock modeling
    • Bioactive
    • Ile-Pro-Pro
    • Tripeptide
    • Val-Pro-Pro
    • Vascular function

    Publication forum classification

    • No publication forum level

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