title: Synthesis and characterization of an antibacterial and non-toxic dimeric peptide derived from the C-terminal region of Bothropstoxin-I.
abstract: 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.
authors.affiliation: Instituto de Química, UNESP - Univ. Estadual Paulista, Araraquara, SP, Brazil. Electronic address: drnorival@yahoo.com.
authors.forename: Norival A
authors.initials: NA
authors.lastname: Santos-Filho
authors.affiliation: Instituto de Química, UNESP - Univ. Estadual Paulista, Araraquara, SP, Brazil.
authors.forename: Esteban N
authors.initials: EN
authors.lastname: Lorenzon
authors.affiliation: Faculdade de Ciências Farmacêuticas, UNESP - Univ. Estadual Paulista, Araraquara, SP, Brazil.
authors.forename: Matheus A S
authors.initials: MA
authors.lastname: Ramos
authors.affiliation: Faculdade de Ciências Farmacêuticas, UNESP - Univ. Estadual Paulista, Araraquara, SP, Brazil.
authors.forename: Claudia T
authors.initials: CT
authors.lastname: Santos
authors.affiliation: Instituto de Química, UNESP - Univ. Estadual Paulista, Araraquara, SP, Brazil.
authors.forename: Julia P
authors.initials: JP
authors.lastname: Piccoli
authors.affiliation: Faculdade de Ciências Farmacêuticas, UNESP - Univ. Estadual Paulista, Araraquara, SP, Brazil.
authors.forename: Tais M
authors.initials: TM
authors.lastname: Bauab
authors.affiliation: Faculdade de Ciências Farmacêuticas, UNESP - Univ. Estadual Paulista, Araraquara, SP, Brazil.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Fusco-Almeida
authors.affiliation: Instituto de Química, UNESP - Univ. Estadual Paulista, Araraquara, SP, Brazil. Electronic address: cilli@iq.unesp.br.
authors.forename: Eduardo M
authors.initials: EM
authors.lastname: Cilli
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D002942:Circular Dichroism; D003435:Crotalid Venoms / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D006461:Hemolysis / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D003435:Crotalid Venoms; D010455:Peptides; C078097:bothropstoxin
keywords: (p-BthTX-I)(2); Antimicrobial peptides; BthTX-I; Lys49 PLA(2); Phospholipase; p-BthTX-I