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Protein & Peptide Letters


ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

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

Author(s): Na Dong, Qing-Quan Ma, An-Shan Shan, Yin-Feng Lv, Wanning Hu, Yao Gu and Yu-Zhi Li

Volume 19, Issue 11, 2012

Page: [1212 - 1219] Pages: 8

DOI: 10.2174/092986612803217006

Price: $65


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

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