Evidences for the action mechanism of angiotensin II and its analogs on Plasmodium sporozoite membranes

Evidences for the action mechanism of angiotensin II and its analogs on Plasmodium sporozoite membranes

Author Torossian Torres, Marcelo Der Google Scholar
Silva, Adriana Farias Google Scholar
Alves, Flavio Lopes Autor UNIFESP Google Scholar
Capurro, Margareth Lara Google Scholar
Miranda, Antonio Autor UNIFESP Google Scholar
Cordeiro, Rodrigo Maghdissian Google Scholar
Oliveira Junior, Vani Xavier Google Scholar
Abstract Malaria is an infectious disease responsible for approximately one million deaths annually. Oligopeptides such as angiotensin II (AII) and its analogs are known to have antimalarial effects against Plasmodium gallinaceum and Plasmodium falciparum. However, their mechanism of action is still not fully understood at the molecular level. In the work reported here, we investigated this issue by comparing the antimalarial activity of AII with that of (i) its diastereomer formed by only d-amino acids; (ii) its isomer with reversed sequence; and (iii) its analogs restricted by lactam bridges, the so-called VC5 peptides. Data from fluorescence spectroscopy indicated that the antiplasmodial activities of both all-D-AII and all-D-VC5 were as high as those of the related peptides AII and VC5, respectively. In contrast, retro-AII had no significant effect against P. gallinaceum. Conformational analysis by circular dichroism suggested that AII and its active analogs usually adopted a -turn conformation in different solutions. In the presence of membrane-mimetic micelles, AII had also a -turn conformation, while retro-AII was random. Molecular dynamics simulations demonstrated that the AII chains were slightly more bent than retro-AII at the surface of a model membrane. At the hydrophobic membrane interior, however, the retro-AII chain was severely coiled and rigid. AII was much more flexible and able to experience both straight and coiled conformations. We took it as an indication of the stronger ability of AII to interact with membrane headgroups and promote pore formation. Copyright (c) 2016 European Peptide Society and John Wiley & Sons, Ltd.
Keywords angiotensin II
molecular dynamics
xmlui.dri2xhtml.METS-1.0.item-coverage Hoboken
Language English
Date 2016
Published in Journal Of Peptide Science. Hoboken, v. 22, n. 3, p. 132-142, 2016.
ISSN 1075-2617 (Sherpa/Romeo, impact factor)
Publisher Wiley
Extent 132-142
Origin http://dx.doi.org/10.1002/psc.2849
Access rights Closed access
Type Article
Web of Science ID WOS:000370220200001
URI https://repositorio.unifesp.br/handle/11600/57938

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