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Effects of Amino Acid Deletion on the Antiplasmodial Activity of Angiotensin II
Authors:Luiz Henrique Rodrigues Ferreira  Adriana Farias Silva  Marcelo Der Torossian Torres  Cibele Nicolaski Pedron  Margareth Lara Capurro  Flávio Lopes Alves  Antonio Miranda  Vani Xavier Oliveira Jr
Institution:1. Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Rua Santa Adélia, 166, Santo André, SP, 09210-170, Brazil
2. Instituto de Ciências Biomédicas, Universidade de S?o Paulo, S?o Paulo, SP, Brazil
3. Departamento de Biofísica, Universidade Federal de S?o Paulo, S?o Paulo, SP, Brazil
Abstract:Malaria is an infectious disease for which effective treatment and prevention strategies remain limited. Our group recently reported that angiotensin II (AII) presents antiplasmodial activity and inhibits the development of Plasmodium gallinaceum in Aedes aegypti. However, details concerning role of each amino acid residue in the antiplasmodial activity of the peptide and information about the minimal structure responsible for this activity remain unknown. In this work, we investigated the effects of specific deletions (i.e., mono-, di-, tri- and tetra-deletions) of AII amino acids on the antiplasmodial activity of this molecule. The peptides were synthesized on solid phase method using the t-Boc strategy, purified using high performance liquid chromatography and characterized using mass spectrometry. The lytic activity of the peptides was assessed in vitro using mature sporozoites extracted from the salivary glands of infected Aedes aegypti mosquitoes. The results demonstrate that all of the deletions reduced antiplasmodial activity compared to native AII and that active analogs tend to adopt β-turn conformations; however, the deletion of bulky hydrophobic residues causes greater reductions of bioactivity than the deletion of hydrophilic residues. Corroborating previous studies, we observed that analog extremities are susceptible to changes and can be carefully modified without compromising the activity of this compound. This research contributes to our understanding of the role of each AII amino acid residue in activity against Plasmodium gallinaceum and identifies two short analogs with similar antiplasmodial activity to AII. These analogs may be candidates for additional antimalarial assays because they are inexpensive and easy to synthesize.
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