New linear antiplasmodial peptides related to angiotensin II

Malaria Journal

Research

Adriana Farias Silva¹  Marcelo Der Torossian Torres¹  Vani Xavier Oliveira¹  Antonio Miranda²  Flávio Lopes Alves²  Margareth Lara Capurro³  Leandro de Souza Silva⁴  Ana Acácia de Sá Pinheiro⁴ 

[1] Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Rua Santa Adélia, 166, 09210-170, Santo André, SP, Brazil;Departamento de Biofísica, Universidade Federal de São Paulo, São Paulo, SP, Brazil;Departamento de Parasitologia, Instituto de Ciências Biomédicas II, Universidade de São Paulo, São Paulo, SP, Brazil;Instituto de Biofísica Carlos Chagas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil;

关键词: Angiotensin II;    Antiplasmodial;    Peptides;    Plasmodium falciparum;    Plasmodium gallinaceum;   

DOI  :  10.1186/s12936-015-0974-y

 received in 2015-04-23, accepted in 2015-10-28,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundAntiplasmodial activities of angiotensin II and its analogues have been extensively investigated in Plasmodium gallinaceum and Plasmodium falciparum parasite species. Due to its vasoconstrictor property angiotensin II cannot be used as an anti-malarial drug.MethodsThis work presents the solid-phase syntheses and liquid chromatography and mass spectrometry characterization of ten linear peptides related to angiotensin II against mature P. gallinaceum sporozoites and erythrocyte invasion by P. falciparum. Conformational analyses were performed by circular dichroism. IC50 assays were performed to identify the ideal concentration used on the biological tests and haemolytical erythrocytic assays were made to verify the viability of the biological experiments. The contractile responses of the analogues were made to evaluate if they are promising candidates to be applied as antiplasmodial drugs.ResultsThe results indicate two short-peptides constituted by hydrophobic residues (5 and 6) with antiplasmodial activity in these models, 89 and 94 % of biological activity against P. gallinaceum sporozoite, respectively, and around 50 % of activity against P. falciparum. Circular dichroism spectra suggested that all the peptides adopted β-turn conformation in different solutions, except peptide 3. Besides the biological assays IC50, the haemolysis assays and contractile response activities were applied for peptides 5 and 6, which did not present expressive results.ConclusionsThe hydrophobic portion and the arginine, tyrosine, proline, and phenylalanine, when present on peptide primary sequence, tend to increase the antiplasmodial activity. This class of peptides can be explored, as anti-malarial drugs, after in vivo model tests.Graphical abstract:The most active peptide presented 94 % activity on P. gallinaceum sporozoites and 53 % inhibited P. falciparum ring forms invasion

【 授权许可】

CC BY   
© Silva et al. 2015