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

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dc.citation.volume7
dc.contributor.authorSilva, Adriana Farias
dc.contributor.authorTorossian Torres, Marcelo Der
dc.contributor.authorSilva, Leandro Souza
dc.contributor.authorAlves, Flavio Lopes [UNIFESP]
dc.contributor.authorde Sa Pinheiro, Ana Acacia
dc.contributor.authorMiranda, Antonio [UNIFESP]
dc.contributor.authorCapurro, Margareth Lara
dc.contributor.authorde la Fuente-Nunez, Cesar
dc.contributor.authorOliveira, Vani Xavier, Jr.
dc.coverageLondon
dc.date.accessioned2020-08-04T13:39:48Z
dc.date.available2020-08-04T13:39:48Z
dc.date.issued2017
dc.description.abstractAngiotensin 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.en
dc.description.affiliationUniv Fed ABC, Ctr Ciencias Nat & Humanas, Santo Andre, SP, Brazil
dc.description.affiliationMIT, Synthet Biol Grp, Synthet Biol Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA
dc.description.affiliationMIT, Elect Res Lab, Cambridge, MA 02139 USA
dc.description.affiliationMIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA
dc.description.affiliationMIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA
dc.description.affiliationBroad Inst MIT & Harvard, Cambridge, MA 02142 USA
dc.description.affiliationCtr Microbiome Informat & Therapeut, Cambridge, MA 02139 USA
dc.description.affiliationUniv Fed Rio de Janeiro, Inst Biofis Carlos Chagas, Rio De Janeiro, RJ, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biofis, Sao Paulo, Brazil
dc.description.affiliationUniv Sao Paulo, Inst Ciencias Biomed 2, Dept Parasitol, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Biofis, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipCoordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
dc.description.sponsorshipFundacao de Amparo a Pesquisa do Estado de Sao Paulo, (FAPESP)
dc.description.sponsorshipRamon Areces Foundation (Spain)
dc.description.sponsorshipIDFAPESP: 2011/10823-9
dc.description.sponsorshipIDFAPESP: 2014/12938-6
dc.description.sponsorshipIDFAPESP: 2011/11348-2
dc.description.sponsorshipIDFAPESP: 2014/04507-5
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1038/s41598-017-14642-z
dc.identifier.citationScientific Reports. London, v. 7, p. -, 2017.
dc.identifier.doi10.1038/s41598-017-14642-z
dc.identifier.fileWOS000414131700019.pdf
dc.identifier.issn2045-2322
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/57130
dc.identifier.wosWOS:000414131700019
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofScientific Reports
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleAngiotensin II-derived constrained peptides with antiplasmodial activity and suppressed vasoconstrictionen
dc.typeinfo:eu-repo/semantics/article
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