Novel Design of Short Antimicrobial Peptides Derived from the Bactericidal Domain of Avian β-defensin-4

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Abstract:

Short antimicrobial peptides were designed and synthesized by C-terminal truncation and residue substitution of avian β-defensin-4. The biological activity of these peptides was examined to elucidate the quantitative structureactivity relationships and find a lead peptide for the development of a novel antimicrobial peptide. The results showed that the truncation of the avian β-defensin-4 eliminated the hemolysis of the peptide. The GLI13 derivative, developed by substituting the Cys of the truncated peptide with Ile, led to increased antimicrobial activity. These results suggest that the peptides with antimicrobial activity can be derived by truncating the avian β-defensin-4. We further developed the GLI13 derivative with an increased net charge by residue substitution. The results showed that the GLI13-5 with 5 net charges had the highest cell selectivty. An increase in the net charge from 6 to 8 did not result in the improvement of antimicrobial potency. Membrane-simulating experiments showed that the peptides preferentially bound to negatively charged phospholipids over zwitterionic phospholipids, which led to greater cell selectivity. A membrane depolarization assay showed that GLI13-5 killed bacteria by targeting the cytoplasmic membrane. These results suggest that the short peptide developed by truncation of linear β-defensin may be a promising candidate for future antibacterial agents.

Keywords: Antimicrobial peptides; avian β-defensin-4; cell selectivity; liposomes

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986612803217006

Publication date: November 1, 2012

More about this publication?
  • Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.
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