Angiotensin II-derived constrained peptides with antiplasmodial activity and suppressed vasoconstriction

Angiotensin II-derived constrained peptides with antiplasmodial activity and suppressed vasoconstriction

Author Silva, Adriana Farias Google Scholar
Torossian Torres, Marcelo Der Google Scholar
Silva, Leandro Souza Google Scholar
Alves, Flavio Lopes Autor UNIFESP Google Scholar
de Sa Pinheiro, Ana Acacia Google Scholar
Miranda, Antonio Autor UNIFESP Google Scholar
Capurro, Margareth Lara Google Scholar
de la Fuente-Nunez, Cesar Google Scholar
Oliveira, Vani Xavier, Jr. Google Scholar
Abstract Angiotensin II (Ang II) is a natural mammalian hormone that has been described to exhibit antiplasmodial activity therefore constituting a promising alternative for the treatment of malaria. Despite its promise, the development of Ang II as an antimalarial is limited by its potent induction of vasoconstriction and its rapid degradation within minutes. Here, we used peptide design to perform targeted chemical modifications to Ang II to generate conformationally restricted (disulfide-crosslinked) peptide derivatives with suppressed vasoconstrictor activity and increased stability. Designed constrained peptides were synthesized chemically and then tested for antiplasmodial activity. Two lead constrained peptides were identified (i.e., peptides 1 and 2), each composed of 10 amino acid residues. These peptides exhibited very promising activity in both our Plasmodium gallinaceum (> 80%) and Plasmodium falciparum (> 40%) models, an activity that was equivalent to that of Ang II, and led to complete suppression of vasoconstriction. In addition, peptide 5 exhibited selective activity towards the pre-erythrocytic stage (98% of activity against P. gallinaceum), thus suggesting that it may be possible to design peptides that target specific stages of the malaria life cycle. The Ang II derived stable scaffolds presented here may provide the basis for development of a new generation of peptide-based drugs for the treatment of malaria.
xmlui.dri2xhtml.METS-1.0.item-coverage London
Language English
Sponsor Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, (FAPESP)
Ramon Areces Foundation (Spain)
Grant number FAPESP: 2011/10823-9
FAPESP: 2014/12938-6
FAPESP: 2011/11348-2
FAPESP: 2014/04507-5
Date 2017
Published in Scientific Reports. London, v. 7, p. -, 2017.
ISSN 2045-2322 (Sherpa/Romeo, impact factor)
Publisher Nature Publishing Group
Extent -
Origin http://dx.doi.org/10.1038/s41598-017-14642-z
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000414131700019
URI https://repositorio.unifesp.br/handle/11600/57130

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