Antiplasmodial activity study of angiotensin II via Ala scan analogs

Antiplasmodial activity study of angiotensin II via Ala scan analogs

Author Silva, Adriana Farias Google Scholar
Bastos, Erick Leite Google Scholar
Torres, Marcelo Der Torossian Google Scholar
Costa-da-Silva, Andre Luis Google Scholar
Ioshino, Rafaella Sayuri Google Scholar
Capurro, Margareth Lara Google Scholar
Alves, Flavio Lopes Autor UNIFESP Google Scholar
Miranda, Antonio Autor UNIFESP Google Scholar
Fischer Vieira, Renata de Freitas Autor UNIFESP Google Scholar
Oliveira, Vani Xavier Google Scholar
Institution Universidade Federal do ABC (UFABC)
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract Angiotensin II (AII) as well as analog peptides shows antimalarial activity against Plasmodium gallinaceum and Plasmodium falciparum, but the exact mechanism of action is still unknown. This work presents the solid-phase synthesis and characterization of eight peptides corresponding to the alanine scanning series of AII plus the amide-capped derivative and the evaluation of the antiplasmodial activity of these peptides against mature P. gallinaceum sporozoites. the Ala screening data indicates that the replacement of either the Ile(5) or the His(6) residues causes minor effects on the in vitro antiplasmodial activity compared with AII, i.e. AII (88%), [Ala(6)]-AII (79%), and [Ala(5)]-AII (75%). Analogs [Ala(3)]-AII, [Ala(1)]-AII, and AII-NH2 showed antiplasmodial activity around 65%, whereas the activity of the [Ala(8)]-AII, [Ala(7)]-AII, [Ala(4)]-AII, and [Ala(2)]-AII analogs is lower than 45%. Circular dichroism data suggest that AII and the most active analogs adopt a beta-fold conformation in different solutions. All AII analogs, except [Ala(4)]-AII and [Ala(8)]-AII, show contractile responses and interact with the AT(1) receptor, [Ala(5)]-AII and [Ala(6)]-AII. in conclusion, this approach is helpful to understand the contribution of each amino acid residue to the bioactivity of AII, opening new perspectives toward the design of new sporozoiticidal compounds. Copyright (C) 2014 European Peptide Society and John Wiley & Sons, Ltd.
Keywords malaria
angiotensin II
sporozoites
Plasmodium gallinaceum
SPPS
structure
activity relationship
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Grant number FAPESP: 2008/51869-9
FAPESP: 2011/10823-9
FAPESP: 2011/23036-5
CNPq: 304887/2010-2
CAPES: PE/2007
Date 2014-08-01
Published in Journal of Peptide Science. Hoboken: Wiley-Blackwell, v. 20, n. 8, p. 640-648, 2014.
ISSN 1075-2617 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 640-648
Origin http://dx.doi.org/10.1002/psc.2641
Access rights Closed access
Type Article
Web of Science ID WOS:000340423300006
URI http://repositorio.unifesp.br/handle/11600/38027

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