Title:Novel Design of Short Antimicrobial Peptides Derived from the Bactericidal Domain of Avian β-defensin-4
VOLUME: 19 ISSUE: 11
Author(s):Na Dong, Qing-Quan Ma, An-Shan Shan, Yin-Feng Lv, Wanning Hu, Yao Gu and Yu-Zhi Li
Affiliation:Institute of Animal Nutrition, Northeast Agricultural University, Harbin, P.R. China, 150030.
Keywords:Antimicrobial peptides, avian β-defensin-4, cell selectivity, liposomes
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.
