We report a biomimetic approach, inspired by polyvalency, to design potent inhibitors of anthrax toxin. Since the major symptoms and death from anthrax are due primarily to the action of anthrax toxin, the toxin is a prime target for therapeutic intervention. We have designed potent liposome-based anthrax toxin inhibitors, and demonstrated that statistical pattern matching significantly enhances the potency of these inhibitors. We functionalized liposomes with an inhibitory peptide at different densities and observed a transition in potency at an inter-peptide separation that matches the distance between ligand-binding sites on the heptameric component of anthrax toxin. Pattern-matched polyvalent liposomes inhibited anthrax toxin in vitro at concentrations four orders of magnitude lower than the corresponding monovalent peptide, and neutralized this toxin in vivo. We have also designed biomimetic inhibitors inspired by lipid rafts, as well as inhibitors that target the cellular receptor for anthrax toxin. These biomimetic anthrax toxin inhibitors may enable the successful treatment of anthrax during the later stages of the disease when antibiotic treatment is ineffective.

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