Antimicrobial peptides conjugated with fatty acids on the side chain of D-amino acid promises antimicrobial potency against multidrug-resistant bacteria.
Eur J Pharm Sci
; 141: 105123, 2020 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-31676352
ABSTRACT
With the alarming burden of antibiotic resistance, antimicrobial peptides (AMPs) seem to be novel antimicrobial alternatives for infection treatment due to their rapid broad-spectrum antimicrobial activity and low tendency for bacterial resistance. To obtain promising AMPs, a series of new peptides were designed and synthesized by conjugating various lengths of fatty acid chains onto the side chain of the position 4 or 7 D-amino acid of Ano-D4,7 (analogue of anoplin with D-amino acid substitutions at positions 4 and 7). The new peptides exhibited excellent antimicrobial activity against a range of bacteria, especially multidrug-resistant bacteria in contrast to conventional antibiotics. Moreover, the new peptides conjugated with fatty acid chains ranging from 8 to 12 carbons in length presented preferable antimicrobial selectivity and anti-biofilm activity. Additionally, the new peptides also exerted high stability to trypsin, serum, salts and different pH environments. Most notably, the new peptides showed a low tendency to develop bacterial resistance and they displayed optimal antimicrobial activity against the obtained resistant strains. Furthermore, the results from the outer/inner membrane permeabilization and cytoplasmic membrane depolarization assays and flow cytometry and scanning electron microscopy analyses demonstrated that the new peptides exert antimicrobial effects by typical non-receptor-mediated membrane mechanisms, as well as intracellular targets characterized by gel retardation and reactive oxygen species (ROS) generation assays. Furthermore, the new peptides presented remarkable in vivo antimicrobial potency, anti-inflammatory activity, and endotoxin neutralization. Collectively, the conjugation of fatty acids to the side chains of D-amino acids is a potential strategy for designing hopeful antimicrobial alternatives to tackle the risk of bacterial resistance.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Ácidos Graxos
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Aminoácidos
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Antibacterianos
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article