| Texto completo | |
| Autor(es): |
Silva, Adriana Farias
[1]
;
Torossian Torres, Marcelo Der
[2, 3, 1, 4, 5, 6, 7]
;
Silva, Leandro Souza
[8]
;
Alves, Flavio Lopes
[9]
;
de Sa Pinheiro, Ana Acacia
[8]
;
Miranda, Antonio
[9]
;
Capurro, Margareth Lara
[10]
;
de la Fuente-Nunez, Cesar
[2, 3, 4, 5, 6, 7]
;
Oliveira, Jr., Vani Xavier
[1]
Número total de Autores: 9
|
| Afiliação do(s) autor(es): | [1] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Santo Andre, SP - Brazil
[2] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 - USA
[3] MIT, Elect Res Lab, Cambridge, MA 02139 - USA
[4] Broad Inst MIT & Harvard, Cambridge, MA 02142 - USA
[5] MIT, Synthet Biol Grp, Synthet Biol Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 - USA
[6] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 - USA
[7] Ctr Microbiome Informat & Therapeut, Cambridge, MA 02139 - USA
[8] Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas, Rio De Janeiro, RJ - Brazil
[9] Univ Fed Sao Paulo, Dept Biofis, Sao Paulo - Brazil
[10] Univ Sao Paulo, Inst Ciencias Biomed 2, Dept Parasitol, Sao Paulo, SP - Brazil
Número total de Afiliações: 10
|
| Tipo de documento: | Artigo Científico |
| Fonte: | SCIENTIFIC REPORTS; v. 7, OCT 30 2017. |
| Citações Web of Science: | 4 |
| Resumo | |
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. (AU) | |
| Processo FAPESP: | 11/10823-9 - Compostos antimaláricos derivados da angiotensina II |
| Beneficiário: | Vani Xavier de Oliveira Junior |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |
| Processo FAPESP: | 11/11348-2 - Peptídeos Antimaláricos Derivados da Angiotensina II |
| Beneficiário: | Adriana Farias da Silva |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 14/04507-5 - Aplicações biológicas de novos peptídeos antimicrobianos |
| Beneficiário: | Marcelo Der Torossian Torres |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 14/12938-6 - Peptídeos biologicamente ativos em micro-organismos patogênicos |
| Beneficiário: | Vani Xavier de Oliveira Junior |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |