Antiplasmodial activity study of angiotensin II via Ala scan analogs. (9th May 2014)

• Record Type: Journal Article
• Authors: Silva, Adriana Farias; Bastos, Erick Leite; Torres, Marcelo Der Torossian; Costa‐da‐Silva, André Luis; Ioshino, Rafaella Sayuri; Capurro, Margareth Lara; Alves, Flávio Lopes; Miranda, Antonio; de Freitas Fischer Vieira, Renata; Oliveira, Vani Xavier
• Is Part Of: Journal of peptide science. Volume 20:Number 8(2014:Aug.)
• Page Start: 640
• Page End: 648
• Publication Date: 2014-05-09
• Subjects: Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.2641
• Languages: English
• ISSNs: 1075-2617

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Angiotensin II (AII) as well as analog peptides shows antimalarial activity against <italic>Plasmodium gallinaceum</italic> and <italic>Plasmodium falciparum</italic>, 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 <italic>P. gallinaceum</italic> sporozoites. The Ala screening data indicates that the replacement of either the Ile<sup>5</sup> or the His<sup>6</sup> residues causes minor effects on the <italic>in vitro</italic> antiplasmodial activity compared with AII, i.e. AII (88%), [Ala<sup>6</sup>]‐AII (79%), and [Ala<sup>5</sup>]‐AII (75%). Analogs [Ala<sup>3</sup>]‐AII, [Ala<sup>1</sup>]‐AII, and AII‐NH<sub>2</sub> showed antiplasmodial activity around 65%, whereas the activity of the [Ala<sup>8</sup>]‐AII, [Ala<sup>7</sup>]‐AII, [Ala<sup>4</sup>]‐AII, and [Ala<sup>2</sup>]‐AII analogs is lower than 45%. Circular dichroism data suggest that AII and the most active analogs adopt a <italic>β</italic>‐fold conformation in different solutions. All AII analogs, except [Ala<sup>4</sup>]‐AII and [Ala<sup>8</sup>]‐AII, show contractile responses and interact with the AT<sub>1</sub> receptor, [Ala<sup>5</sup>]‐AII and [Ala<sup>6</sup>]‐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 © 2014 European Peptide Society and John Wiley & Sons, Ltd.</p> </abstract>