Synthesis and characterization of an antibacterial and non-toxic dimeric peptide derived from the C-terminal region of Bothropstoxin-I

Autor(es)

Santos-Filho, Norival A. ^[1] ; Lorenzon, Esteban N. ^[1] ; Ramos, Matheus A. S. ^[2] ; Santos, Claudia T. ^[2] ; Piccoli, Julia P. ^[1] ; Bauab, Tais M. ^[2] ; Fusco-Almeida, Ana M. ^[2] ; Cilli, Eduardo M. ^[1]

Afiliação do(s) autor(es)

^[1] UNESP Univ Estadual Paulista, Inst Quim, Araraquara, SP - Brazil

^[2] UNESP Univ Estadual Paulista, Fac Ciencias Farmaceut, Araraquara, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Toxicon; v. 103, p. 160-168, SEP 1 2015.
• Citações Web of Science: 14

Resumo

Infectious diseases are among the leading global causes of death, increasing the search for novel antibacterial agents. Among these, biologically active peptides are an excellent research tool. Using solid-phase peptide synthesis (SPPS), this work aimed to synthesize the peptide derived from the C-terminal region of Bothropstoxin-I (BthTX-I) (p-BthTX-I, sequence: KKYRYHLKPFCKK), and its disulfide-linked dimeric form, obtained via air oxidation (p-BthTX-I)(2). Two other peptides were synthesized to evaluate the dimerization effect on antimicrobial activity. In both sequences, the cysteine (Cys) residue was replaced by the serine (Ser) residue, differing, however, in their C-terminus position. The antimicrobial activity of the peptides against gram-negative (Escherichia (E.) coli) and gram-positive (Staphylococcus (S.) aureus) bacteria and yeast (Candida (C.) albicans) was evaluated. Interestingly, only peptides containing the Cys residue showed antimicrobial activity, suggesting the importance of Cys residue and its dimerization for the observed activity. Apparently, p-BthTX-I and (p-BthTX-I)(2) did not promote lysis or form pores and were not able to interact with membranes. Furthermore, they neither showed antifungal activity against C. albicans nor toxicity against erythrocytes, epithelial cells, or macrophages, indicating a potential specificity against prokaryotic cells. (C) 2015 Elsevier Ltd. All rights reserved. (AU)

• Processo FAPESP: 14/05538-1 - Síntese, caracterização, estudo do mecanismo de ação e análise de métodos de liberação do peptídeo pBthTX-I, nas formas monoméricas e diméricas
• Beneficiário: Norival Alves Santos Filho
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado