Angiotensin II-derived constrained peptides with antiplasmodial activity and suppressed vasoconstriction
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Silva_et_al-2017-Scientific_Reports.pdf
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Author(s)
Silva, Adriana Farias
Silva, Leandro Souza
Alves, Flavio Lopes
de Sá Pinheiro, Ana Acácia
Miranda, Antonio
Capurro, Margareth Lara
Oliveira, Vani Xavier
Der Torossian Torres, Marcelo
de la Fuente Nunez, Cesar
Date Issued
October 2017
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Silva, Adriana Farias et al. “Angiotensin II-Derived Constrained Peptides with Antiplasmodial Activity and Suppressed Vasoconstriction.” Scientific Reports 7, 1 (October 2017): 14326 © 2017 The Author(s)
Version
Final published version
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.
MIT Department
MIT Synthetic Biology Center
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Massachusetts Institute of Technology. Research Laboratory of Electronics
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DOI of Published Version
https://doi.org/10.1038/s41598-017-14642-z
