| Texto completo | |
| Autor(es): Mostrar menos - |
Pedron, Cibele Nicolaski
;
Torres, Marcelo Der Torossian
;
Oliveira, Cyntia Silva
;
Silva, Adriana Farias
;
Andrade, Gislaine Patricia
;
Wang, Yiming
;
Pinhal, Maria Aparecida Silva
;
Cerchiaro, Giselle
;
da Silva Jr, Pedro Ismael
;
da Silva, Fernanda Dias
;
Radhakrishnan, Ravi
;
de la Fuente-Nunez, Cesar
;
Oliveira Jr, Vani Xavier
Número total de Autores: 13
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| Tipo de documento: | Artigo Científico |
| Fonte: | COMMUNICATIONS BIOLOGY; v. 6, n. 1, p. 13-pg., 2023-10-19. |
| Resumo | |
The physicochemical and structural properties of antimicrobial peptides (AMPs) determine their mechanism of action and biological function. However, the development of AMPs as therapeutic drugs has been traditionally limited by their toxicity for human cells. Tuning the physicochemical properties of such molecules may abolish toxicity and yield synthetic molecules displaying optimal safety profiles and enhanced antimicrobial activity. Here, natural peptides were modified to improve their activity by the hybridization of sequences from two different active peptide sequences. Hybrid AMPs (hAMPs) were generated by combining the amphipathic faces of the highly toxic peptide VmCT1, derived from scorpion venom, with parts of four other naturally occurring peptides having high antimicrobial activity and low toxicity against human cells. This strategy led to the design of seven synthetic bioactive variants, all of which preserved their structure and presented increased antimicrobial activity (3.1-128 mu mol L-1). Five of the peptides (three being hAMPs) presented high antiplasmodial at 0.8 mu mol L-1, and virtually no undesired toxic effects against red blood cells. In sum, we demonstrate that peptide hybridization is an effective strategy for redirecting biological activity to generate novel bioactive molecules with desired properties. A hybrid antimicrobial peptide (AMP) design derived from scorpion venom and parts of other naturally occurring AMPs leads to AMPs with increased antimicrobial activity and minimal toxicity in a mouse infection model and red blood cells. (AU) | |
| Processo FAPESP: | 17/03046-2 - Peptídeos biologicamente ativos em micro-organismos patogênicos e em células tumorais |
| Beneficiário: | Vani Xavier de Oliveira Junior |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |