Síntesis de péptidos derivados de la lactoferricina bovina y evaluación de su actividad antibacteriana
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La resistencia a los agentes antimicrobianos es un problema de salud pública a nivel mundial. Los péptidos antimicrobianos catiónicos (AMPs) son moléculas potenciales para el desarrollo de nuevos agentes terapéuticos contra infecciones causadas por patógenos resistentes. En este trabajo se diseñaron, purificaron y caracterizaron péptidos derivados de LfcinB 17-31 (17FKCRRWQWRMKKLGA31); se construyó una librería peptídica removiendo sistemáticamente los residuos (N o C-terminal) que flaquean el motivo RRWQWR que corresponde a la secuencia mínima reportada con actividad antimicrobiana. Se incluyó también para el estudio (i) un péptido que contiene una Alanina en lugar de Cisteína ([Ala19]-LfcinB 17-31) y (ii) péptidos polivalentes que contienen la secuencia RRWQWR y un aminoácido no natural (ácido aminocaproico). Para cada péptido se ensayó la actividad antibacteriana frente a E. coli ATCC 25922 y S. aureus ATCC 25923. Se estableció que los péptidos LfcinB 17-26 (17FKCRRWQWRM26) y LfcinB 17-25 ( 17FKCRRWQWR25) presentaban la mayor actividad contra S. aureus ATCC 25923 y E. coli ATCC 25922, respectivamente. Por otra parte, los péptidos polivalentes: el dímero (FKARRWQWRMKKLGA)2K-Ahx-C y el tetrámero (RRWQWR)2K-Ahx-C)2, mostraron la mayor actividad antibacteriana, indicando que múltiples copias de la secuencia aumentan la actividad. Nuestros resultados sugieren que el diseño de péptidos lineales y polivalentes es una estrategia versátil para identificar secuencias potenciales en el desarrollo de agentes terapéuticos peptídicos.
Abstract. Resistance to antimicrobial agents is a public health problem worldwide. Cationic antimicrobial peptides (AMPs) are potential molecules to develop new therapeutic agents against infections caused by resistant pathogens. In this work, peptides derived from LfcinB 17-31 (17FKCRRWQWRMKKLGA31) were designed, purified and characterized. A peptide library was constructed by systemically removing the flanking residues (N or C-terminal) of the RRWQWR sequence that corresponds to minimal antimicrobial motif. For this research, it was also included (i) a peptide containing an Ala instead of Cys ([Ala19]-LfcinB 17-31) and (ii) polyvalent peptides containing the RRWQWR sequence and a non- natural amino acid (aminocaproic acid). For each peptide the antibacterial activity was tested against E. coli ATCC 25922 and S. aureus ATCC 25923. We established that peptides LfcinB 17- 26 ( 17FKCRRWQWRM26) and LfcinB 17-25 ( 17FKCRRWQWR25) presented the bigger activity against S. aureus ATCC 25923 and E. coli ATCC 25922, respectively. By the other hand, polyvalent peptides, the dimer (FKARRWQWRMKKLGA)2K-Ahx-C, and tetramer ((RRWQWR) 2K-Ahx-C)2, showed the highest antibacterial activity, indicating that the multiple copies of the sequence increase the activity. Our results suggest that the design of lineal and polyvalent peptides is a versatile strategy to identify potential sequences to developing peptide therapeutics.
Abstract. Resistance to antimicrobial agents is a public health problem worldwide. Cationic antimicrobial peptides (AMPs) are potential molecules to develop new therapeutic agents against infections caused by resistant pathogens. In this work, peptides derived from LfcinB 17-31 (17FKCRRWQWRMKKLGA31) were designed, purified and characterized. A peptide library was constructed by systemically removing the flanking residues (N or C-terminal) of the RRWQWR sequence that corresponds to minimal antimicrobial motif. For this research, it was also included (i) a peptide containing an Ala instead of Cys ([Ala19]-LfcinB 17-31) and (ii) polyvalent peptides containing the RRWQWR sequence and a non- natural amino acid (aminocaproic acid). For each peptide the antibacterial activity was tested against E. coli ATCC 25922 and S. aureus ATCC 25923. We established that peptides LfcinB 17- 26 ( 17FKCRRWQWRM26) and LfcinB 17-25 ( 17FKCRRWQWR25) presented the bigger activity against S. aureus ATCC 25923 and E. coli ATCC 25922, respectively. By the other hand, polyvalent peptides, the dimer (FKARRWQWRMKKLGA)2K-Ahx-C, and tetramer ((RRWQWR) 2K-Ahx-C)2, showed the highest antibacterial activity, indicating that the multiple copies of the sequence increase the activity. Our results suggest that the design of lineal and polyvalent peptides is a versatile strategy to identify potential sequences to developing peptide therapeutics.