Anthrax is a deadly disease that could potentially be used in biological terrorism or warfare. The bacterium that causes anthrax produces a toxin that is extremely deadly, causing a disease that is invariably fatal if not treated immediately with antibiotics. Now, a group of researchers led by John Collier and George Whitesides may have come up with a means of combating the toxin (Nature Biotechnology, Vol. 19, No. 10, 01 Oct 2001). They have designed a polyvalent inhibitor (PVI) of the toxin that protects rats for at least one week after receiving doses of toxin 10-times the minimum lethal amount. Rats exposed to the toxin in the absence of PVI normally survive for only a few hours.
Using their knowledge that the anthrax bacterium secretes three nontoxic proteins that assemble into toxin complexes on mammalian cell membranes, Collier and his team screened peptide libraries for an inhibitor that prevents the toxin assembly process. Their screen identified a 12-amino acid peptide that inhibited assembly, albeit weakly. They then set about creating a PVI by covalently linking multiple copies of this inhibitor to a flexible polyacrylamide backbone, increasing the inhibitory activity of the peptide by about 7,500-fold.
Their method of developing synthetic, polymeric, polyvalent inhibitors of protein - protein interactions may also turn out to be a useful tool for increasing the therapeutic potency of drugs such as antitumor peptides, growth factor receptor agonists, or molecules with related mechanisms of action.
R. John Collier
Department of Microbiology and Molecular Genetics
Harvard Medical School
200 Longwood Avenue
Boston, MA 02115
(C) Nature Biotechnology press release.
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