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Secramine, a synthetic inhibitor of Cdc42, traps a fluorescent protein (shown above in green) in the Golgi apparatus (top).

(Photo by Tom Kirchhausen)

Synthetic molecule blocks exit from cell organelle

December 16, 2005

The ubiquitous, small GTPases are a family of signal transduction molecules that play crucial roles in numerous biological processes, including cell motility and division. Though scientists have eyed these proteins as potential therapeutic targets for years, inhibitors of GTPases have proven exceedingly difficult to develop; currently there are only a handful in existence. But in a Nov. 20, 2005 advanced online publication in Nature Chemical Biology,Tom Kirchhausen, Matthew Shair, and Henry Pelish have revealed a new class of GTPase inhibitor. They have synthesized secramine, a small molecule that blocks the GTPase Cdc42, which is crucial for vesicular transport and cell migration. The finding provides a new means to study protein traffic from the Golgi apparatus and offers hope that unique and specific GTPase inhibitors might one day be used to treat disease.

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