2004;101:13147C13151. glycol linker of a proper length. The causing heptavalent inhibitors neutralized anthrax lethal toxin both in vitro and in vivo and demonstrated appreciable balance in serum. Provided the natural biocompatibility of cyclodextrin and polyethylene glycol, these potent well-defined heptavalent inhibitors show considerable promise as anthrax anti-toxins. by incubating RAW264.7 cells with a mixture of PA and LF in the presence of several concentrations of the inhibitor. The heptavalent molecule could inhibit cytotoxicity with a half-maximal inhibitory concentration (IC50) of ca. 10 nM on a per-peptide basis (Fig. 6A). Heptavalent molecules presenting Seocalcitol only thioglycerol showed no inhibitory activity (Fig. 6A), and the monovalent peptide did not inhibit cytotoxicity at concentrations as high as 2 mM. The heptavalent inhibitor therefore provided a more than 100,000-fold enhancement in the activity of this peptide. To test whether the well-defined heptavalent inhibitor based on the PEG11 linker was resistant to proteolytic degradation, we also incubated the inhibitor with 80% serum at 37 C. Samples were withdrawn at various time intervals and Pdgfra their inhibitory activity was decided using the cytotoxicity assay. As seen in Physique 6B, the heptavalent inhibitor did not show any significant loss in activity over a three day period. Open in a separate window Physique 6 Characterization of a well-defined heptavalent anthrax toxin inhibitor. and and Seocalcitol showed appreciable stability in serum. Given the inherent biocompatibility of cyclodextrin and polyethylene glycol, these potent well-defined heptavalent anti-toxins might serve as valuable adjuncts to antibiotics for the treatment of anthrax. 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