Figure 4.

Helix/sheet topomimetics protect mice from LPS endotoxin. Three helix/sheet topomimetics (5, 13 and 17) were used in mouse endotoxemia models to assess in vivo efficacy. In three separate studies, these compounds were tested against LPS derived from E. coli serotype 0111 :B4, E. coli serotype 055:B5 LPS, and Salmonella. The compounds (in a final concentration of 2 % DMSO v/v), were first mixed individually with LPS, and incubated for 30 minutes prior to i.p. injection into C57/BL6 mice (n = 4–8/group). The control mice were treated with DMSO (2% v/v) alone. Each mouse received a lethal dose of LPS, with or without one of the compounds. (A) Survival of mice after being challenged with 600 μ1 LPS form E. coli serotype 055:B5 with or without one of the compounds. The survival percentage of treatment with compound 5 and 13 are significantly significant (p = 0.03 and 0.006 respectively). (B) Survival of mice after being challenged with 500 μl LPS form E. coli serotype 0111:B4 with or without one of the compounds. The survival percentage of treatment with compound 13 is significantly increased (p = 1.3 10⁻⁵). (C) Survival of mice after being challenged with 600 μ1 LPS form Salmonella with or without one of the compounds. The survival percentage of treatment with compound 17, 5 and 13 are significantly increased (p = 9×l0⁻⁸, 0.008 and 0.002 respectively). In all panels, symbols are defined as: control (□), 5 (•), 17 (π), 13(θ).