Sequestration of bacterial lipopolysaccharide by bis(Args) gemini compounds.
Gemini compounds of the type N(alpha),N(omega)-bis(N(alpha)-lauroyl arginine)alpha,omega-alkylenediamides or bis(Args) bind bacterial lipopolysaccharide and neutralize endotoxic activity in in vitro tumor necrosis factor-alpha and nitric oxide release assays. Sequestration of lipopolysaccharide results in protection in a murine model of endotoxemia. However, the bis(Args) compounds are cytotoxic by virtue of being highly membrane-active. The development of less surface-active analogues may yield potentially therapeutically useful compounds for the treatment of Gram-negative sepsis.
David
Sunil
S
Molecular Biosciences, 4043 Haworth Hall, University of Kansas, Lawrence, KS 66044, USA. sdavid@ku.edu
Pérez
Lourdes
L
Infante
M Rosa
MR
D000577:Amides / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D019446:Endotoxemia / Q000097:blood / Q000188:drug therapy; D004731:Endotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity; D006461:Hemolysis / Q000187:drug effects; D007202:Indicators and Reagents; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D000577:Amides; D004731:Endotoxins; D007202:Indicators and Reagents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C044101:endotoxin, Escherichia coli; D001120:Arginine