Dissection of phospholipases A(2) reveals multifaceted peptides targeting cancer cells, Leishmania and bacteria

Autor(es)

Pena-Carrillo, Maria S. ^[1] ; Pinos-Tamayo, Edgar A. ^[1] ; Mendes, Bruno ^[2] ; Dominguez-Borbor, Cristobal ^[3] ; Proano-Bolanos, Carolina ^[1] ; Miguel, Danilo C. ^[2] ; Almeida, Jose R. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Reg Amazon Ikiam, Biomol Discovery Grp, Km 7 Via Muyuna, Tena, Napo - Ecuador

^[2] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Biol Anim, Campinas, SP - Brazil

^[3] ESPOL Polytech Univ, Escuela Super Politecn Litoral, ESPOL, Ctr Nacl Invest Marinas CENAIM, Campus Gustavo Galindo Km 30 5 Via Perimetral, Guayaquil - Ecuador

• Tipo de documento: Artigo Científico
• Fonte: BIOORGANIC CHEMISTRY; v. 114, SEP 2021.
• Citações Web of Science: 1

Resumo

Cationic peptides bio-inspired by natural toxins have been recognized as an efficient strategy for the treatment of different health problems. Due to the specific interaction with substrates from biological membranes, snake venom phospholipases (PLA(2)s) represent valuable scaffolds for the research and development of short peptides targeting parasites, bacteria, and cancer cells. Considering this, we evaluated the in vitro therapeutic potential of three biomimetic peptides (pCergo, pBmTxJ and pBmje) based on three different amino acid sequences from Asp49 PLA(2)s. First, short amino acid sequences (12-17 in length) derived from these membranolytic toxins were selected using a combination of bioinformatics tools, including AntiCP, AMPA, PepDraw, ToxinPred, and HemoPI. The peptide, from each polypeptide sequence, with the greatest average antimicrobial index, no toxicity, and no hemolysis predicted was synthesized, purified, and characterized. According to in vitro assays performed, pBmje showed moderate cytotoxicity specifically against MCF-7 (breast cancer cells) with an EC50 of 464.85 mu M, whereas pBmTxJ showed an antimicrobial effect against Staphylococcus aureus (ATCC 25923) with an MIC of 37.5 mu M, and pCergo against E. coli (ATCC 25922) with an MIC of 75 mu M. In addition, pCergo showed antileishmanial activity with an EC50 of 93.69 mu M and 110.40 mu M against promastigotes of Leishmania braziliensis and L. amazonensis, respectively. Altogether, these results confirmed the versatility of PLA(2)-derived synthetic peptides, highlighting the relevance of the use of these membrane-interacting toxins as specific archetypes for drug design focused on public health problems. (AU)

• Processo FAPESP: 14/21129-4 - O papel das proteínas ligantes de ácidos graxos na infecção de macrófagos por Leishmania: um alvo potencial para novas drogas contra leishmaniose
• Beneficiário: Danilo Ciccone Miguel
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores