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Biological Chemistry

Small Molecule Found In Cone Snail Arsenal

Natural Products: Although known for their paralyzing polypeptides, cone snails also use a guanine derivative to disable their prey

by Bethany Halford
October 12, 2015 | APPEARED IN VOLUME 93, ISSUE 40

Just before engulfing a tasty meal of a fish or a marine worm, a cone snail paralyzes its prey by injecting it with venom from a harpoonlike tooth. Scientists previously identified the paralyzing compounds in cone snail venom as polypeptides. Some of them have even been developed into pain medication for people, such as the synthetic injectable drug ziconotide (Prialt). Researchers led by University of Utah biologist Baldomero M. Olivera and chemist Eric W. Schmidt now report that polypeptides aren’t the only paralyzing compounds in cone snail venom. They identified a small molecule in two different cone snail species—Conus genuanus and Conus geographus—that causes paralysis in mice when given at nanomolar doses (Org. Lett. 2015, DOI: 10.1021/acs.orglett.5b02389). Olivera and Schmidt’s team determined the compound’s structure and named it genuanine. Genuanine is a guanine derivative and the first small-molecule paralytic to be identified in cone snail venom. The researchers aren’t certain if genuanine is synthesized by the cone snail or its associated bacteria. Nevertheless, they say “it appears that small molecules are important and previously unrecognized contributors to the toxicity of cone snail venom.”

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