Net charge tuning modulates the antiplasmodial and anticancer properties of peptides derived from scorpion venom

Autor(es)

Pedron, Cibele Nicolaski ^{[1, 2]} ; Silva, Adriana Farias ^{[1, 2]} ; Torres, Marcelo Der Torossian ^{[3, 4, 5, 6, 7]} ; de Oliveira, Cyntia Silva ^[2] ; Andrade, Gislaine Patricia ^[1] ; Cerchiaro, Giselle ^[1] ; Pinhal, Maria Aparecida Silva ^[2] ; de la Fuente-Nunez, Cesar ^{[3, 4, 5, 6, 7]} ; Oliveira Junior, Vani Xavier ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Fed ABC, Ctr Ciencias Nat & Humanas, BR-09210580 Santo Andre, SP - Brazil

^[2] Univ Fed Sao Paulo, Dept Biofis, BR-04044020 Sao Paulo, SP - Brazil

^[3] Univ Penn, Dept Psychiat, Inst Translat Med & Therapeut, Machine Biol Grp, Inst Biomed Informat, Perelman Sc, Philadelphia, PA 19102 - USA

^[4] Univ Penn, Dept Microbiol, Inst Translat Med & Therapeut, Machine Biol Grp, Inst Biomed Informat, Perelman Sc, Philadelphia, PA 19102 - USA

^[5] Univ Penn, Sch Engn & Appl Sci, Dept Bioengn, Philadelphia, PA 19102 - USA

^[6] Univ Penn, Sch Engn & Appl Sci, Dept Chem & Biomol Engn, Philadelphia, PA 19102 - USA

^[7] Univ Penn, Penn Inst Computat Sci, Philadelphia, PA 19102 - USA

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PEPTIDE SCIENCE; v. 27, n. 4 JAN 2021.
• Citações Web of Science: 0

Resumo

VmCT1, a linear helical antimicrobial peptide isolated from the venom of the scorpion Vaejovis mexicanus, displays broad spectrum antimicrobial activity against bacteria, fungi, and protozoa. Analogs derived from this peptide containing single Arg-substitutions have been shown to increase antimicrobial and antiparasitic activities against Trypanossoma cruzi. Here, we tested these analogs against malaria, an infectious disease caused by Plasmodium protozoa, and assessed their antitumoral properties. Specifically, we tested VmCT1 synthetic variants {[}Arg](3)-VmCT1-NH2, {[}Arg](7)-VmCT1-NH2, and {[}Arg](11)-VmCT1-NH2, against Plasmodium gallinaceum sporozoites and MCF-7 mammary cancer cells. Our screen identified peptides {[}Arg](3)-VmCT1-NH2 and {[}Arg](7)-VmCT1-NH2 as potent antiplasmodial agents (IC50 of 0.57 and 0.51 mu mol L-1, respectively), whereas {[}Arg](11)-VmCT1-NH2 did not show activity against P. gallinaceum sporozoites. Interestingly, all peptides presented activity against MCF-7 and displayed lower cytotoxicity toward healthy cells. We demonstrate that increasing the net positive charge of VmCT1, through arginine substitutions, modulates the biological properties of this peptide family yielding novel antiplasmodial and antitumoral molecules. (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