Antiplasmodial activity study of angiotensin II via Ala scan analogs

Antiplasmodial activity study of angiotensin II via Ala scan analogs

Autor 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
Instituição Universidade Federal do ABC (UFABC)
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Resumo 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.
Assunto malaria
angiotensin II
sporozoites
Plasmodium gallinaceum
SPPS
structure
activity relationship
Idioma Inglês
Financiador 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)
Número do financiamento FAPESP: 2008/51869-9
FAPESP: 2011/10823-9
FAPESP: 2011/23036-5
CNPq: 304887/2010-2
CAPES: PE/2007
Data 2014-08-01
Publicado em Journal of Peptide Science. Hoboken: Wiley-Blackwell, v. 20, n. 8, p. 640-648, 2014.
ISSN 1075-2617 (Sherpa/Romeo, fator de impacto)
Editor Wiley-Blackwell
Extensão 640-648
Fonte http://dx.doi.org/10.1002/psc.2641
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000340423300006
URI http://repositorio.unifesp.br/handle/11600/38027

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