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George M. Whitesides

R. John Collier

William F. Dietrich

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October 8, 2001
Volume 79, Number 41
CENEAR 79 41 p. 12
ISSN 0009-2347
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Scientists discover a protective gene and a molecule that inhibits the toxin


Two reports on promising efforts to understand and thwart the deadly effects of the toxins produced by the anthrax bacterium come from researchers at Harvard University.

DEADLY The bacterial species that causes anthrax, shown here in a lung capillary, is high on the list of potential biological warfare agents.
Chemist George M. Whitesides, molecular geneticist R. John Collier of Harvard Medical School, and colleagues have designed a molecule that's a reasonably effective inhibitor of anthrax toxin in rats. They screened a peptide library to find a peptide that binds weakly to the cell-binding portion of the anthrax toxin, thereby preventing the toxin from delivering its lethal portion into cells [Nat. Biotech., 19, 958 (2001)]. Reasoning that it's sometimes possible to increase the effectiveness of a weakly binding ligand by presenting a lot of it, the researchers attached many copies of their nonnatural peptide to a flexible polymeric backbone. The resulting molecule could protect rats against 10 times the usual lethal dose of anthrax toxin.

The work is "an important and encouraging step" toward a treatment that blocks the effects of the toxin itself, Whitesides says. But much more work will be needed, including experiments in other model systems, to see whether this approach will lead to an effective drug.

Meanwhile, geneticist William F. Dietrich, also at Harvard Medical School, and colleagues have isolated a gene from inbred mice that are naturally resistant to anthrax toxin [Curr. Biol., 11, 1503, (2001)]. Surprisingly, it's the gene for a motor molecule known as a kinesin, whose function is to ferry proteins around in the cell. For now, it's not at all clear how disrupting this process thwarts anthrax toxin. Humans have their own version of this gene, so efforts will be under way to see if some people have mutant forms that protect them against anthrax. Learning how the protein interferes with anthrax toxin may lead to targets for future drug development, Dietrich suggests.

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