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Appl Environ Microbiol ; 79(10): 3156-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23455341

RESUMO

Antimicrobial resistance is a persistent problem in the public health sphere. However, recent attempts to find effective substitutes to combat infections have been directed at identifying natural antimicrobial peptides in order to circumvent resistance to commercial antibiotics. This study describes the development of synthetic peptides with antimicrobial activity, created in silico by site-directed mutation modeling using wild-type peptides as scaffolds for these mutations. Fragments of antimicrobial peptides were used for modeling with molecular modeling computational tools. To analyze these peptides, a decision tree model, which indicated the action range of peptides on the types of microorganisms on which they can exercise biological activity, was created. The decision tree model was processed using physicochemistry properties from known antimicrobial peptides available at the Antimicrobial Peptide Database (APD). The two most promising peptides were synthesized, and antimicrobial assays showed inhibitory activity against Gram-positive and Gram-negative bacteria. Colossomin C and colossomin D were the most inhibitory peptides at 5 µg/ml against Staphylococcus aureus and Escherichia coli. The methods described in this work and the results obtained are useful for the identification and development of new compounds with antimicrobial activity through the use of computational tools.


Assuntos
Peptídeos Catiônicos Antimicrobianos/síntese química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Árvores de Decisões , Algoritmos , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/genética , Characidae/genética , Biologia Computacional/métodos , Simulação por Computador , Bases de Dados de Proteínas , Escherichia coli/efeitos dos fármacos , Biblioteca Gênica , Interações Hidrofóbicas e Hidrofílicas , Testes de Sensibilidade Microbiana , Mutagênese Sítio-Dirigida , Staphylococcus aureus/efeitos dos fármacos
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