Characterization of a proteolytically stable multifunctional host defense peptidomimetic
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Characterization of a proteolytically stable multifunctional host defense peptidomimetic. / Jahnsen, Rasmus D; Haney, Evan F; Franzyk, Henrik; Hancock, Robert E W.
In: Chemistry & Biology, Vol. 20, No. 10, 10.10.2013, p. 1286-1295.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Characterization of a proteolytically stable multifunctional host defense peptidomimetic
AU - Jahnsen, Rasmus D
AU - Haney, Evan F
AU - Franzyk, Henrik
AU - Hancock, Robert E W
N1 - Copyright © 2013 Elsevier Ltd. All rights reserved.
PY - 2013/10/10
Y1 - 2013/10/10
N2 - The in vitro activity of a host defense peptidomimetic (HDM-4) was investigated. The compound exhibited an antimicrobial activity profile against a range of Gram-negative bacteria. HDM-4 permeabilized the outer membrane and partly depolarized the inner membrane at its minimal inhibitory concentration (MIC). Moreover, it was demonstrated that HDM-4 was distributed widely in the bacterial cell at lethal concentrations, and that it could bind to DNA. It was confirmed that the multimodal action of HDM-4 resulted in it being less likely to lead to resistance development as compared to single-target antibiotics. HDM-4 exhibited multispecies anti-biofilm activity at sub-MIC levels. Furthermore, HDM-4 modulated the immune response by inducing the release of the chemoattractants interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), and MCP-3 from human peripheral blood mononuclear cells. In addition, the compound suppressed lipopolysaccharide-mediated inflammation by reducing the release of the pro-inflammatory cytokines IL-6 and tumor necrosis factor-α.
AB - The in vitro activity of a host defense peptidomimetic (HDM-4) was investigated. The compound exhibited an antimicrobial activity profile against a range of Gram-negative bacteria. HDM-4 permeabilized the outer membrane and partly depolarized the inner membrane at its minimal inhibitory concentration (MIC). Moreover, it was demonstrated that HDM-4 was distributed widely in the bacterial cell at lethal concentrations, and that it could bind to DNA. It was confirmed that the multimodal action of HDM-4 resulted in it being less likely to lead to resistance development as compared to single-target antibiotics. HDM-4 exhibited multispecies anti-biofilm activity at sub-MIC levels. Furthermore, HDM-4 modulated the immune response by inducing the release of the chemoattractants interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), and MCP-3 from human peripheral blood mononuclear cells. In addition, the compound suppressed lipopolysaccharide-mediated inflammation by reducing the release of the pro-inflammatory cytokines IL-6 and tumor necrosis factor-α.
U2 - 10.1016/j.chembiol.2013.09.007
DO - 10.1016/j.chembiol.2013.09.007
M3 - Journal article
C2 - 24120333
VL - 20
SP - 1286
EP - 1295
JO - Chemistry and Biology
JF - Chemistry and Biology
SN - 2451-9448
IS - 10
ER -
ID: 56064391