Novel design of short antimicrobial peptides derived from the bactericidal domain of avian β-defensin-4

Na Dong, Qing Quan Ma, An Shan Shan, Yin Feng Lv, Wanning Hu, Yao Gu, Yu Zhi Li

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1212-1219
Number of pages8
JournalProtein and Peptide Letters
Volume19
Issue number11
DOIs
StatePublished - Nov 1 2012

Keywords

  • Antimicrobial peptides
  • Avian β-defensin-4
  • Cell selectivity
  • Liposomes

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