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

Autor: Torres MD; Universidade Federal do ABC, Centro de Ciências Naturais e Humanas, Santo André, SP, Brazil., Silva AF; Universidade Federal do ABC, Centro de Ciências Naturais e Humanas, Santo André, SP, Brazil., Alves FL; Universidade Federal de São Paulo, Departamento de Biofísica, São Paulo, SP, Brazil., Capurro ML; Universidade de São Paulo, Instituto de Ciências Biomédicas II, São Paulo, SP, Brazil., Miranda A; Universidade Federal de São Paulo, Departamento de Biofísica, São Paulo, SP, Brazil., Cordeiro RM; Universidade Federal do ABC, Centro de Ciências Naturais e Humanas, Santo André, SP, Brazil., Oliveira Junior VX; Universidade Federal do ABC, Centro de Ciências Naturais e Humanas, Santo André, SP, Brazil.
Jazyk: angličtina
Zdroj: Journal of peptide science : an official publication of the European Peptide Society [J Pept Sci] 2016 Mar; Vol. 22 (3), pp. 132-42.
DOI: 10.1002/psc.2849
Abstrakt: 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 β-turn conformation in different solutions. In the presence of membrane-mimetic micelles, AII had also a β-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 © 2016 European Peptide Society and John Wiley & Sons, Ltd.)
Databáze: MEDLINE
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