Synthesized spider venom could one day save stroke or smoke-inhalation victims from brain damage, Cornell chemist says

ANAHEIM, Calif. -- A new chemical isolated from spider venom might one day prevent human brain cells from dying after being deprived of oxygen for short periods, a Cornell University chemist believes.

In a talk today (March 23) at the American Chemical Society national meeting at the Anaheim Hilton, Jerrold Meinwald, professor of chemistry biology noted that smoke-inhalation or stroke can cause overproduction of amino-acid neurotransmitters, possibly resulting in brain damage. "What this venom could do is block the effect of the overproduction of some of the neurotransmitters," he said. "In effect, we're turning off the receiver."

The new neuroactive chemical, known as HF-7, was originally isolated from the venom of the funnel-web spider, Hololena curta. The work was a collaboration of chemists at Cornell, Leiden University in the Netherlands, and Cambridge Neuroscience, Inc., a pharmaceutical firm in Cambridge, Mass.

Until the discovery of HF-7, it was thought that all spider venom components were amino-acid based. However, this venom is based on a nucleic acid building block, Meinwald said: "It was a genuine surprise. We had no idea at all that this toxin was made from a nucleic acid component."

Describing his search for this neuroactive chemical, Meinwald said, "Looking for a needle in a haystack is easier. There you just get a big magnet and you'll find it. Looking for this chemical, we didn't know what we'd find. We didn't know what kind of structure we were looking for."

HF-7 works in the brain by blocking one in a family of receptor molecules called kainate receptors, which act as gates in nerve cell membranes. Theoretically, during short bouts of oxygen loss, HF-7 should stave off severe brain damage. However, Meinwald said, it is not clear if the synthesized venom can break through the blood-brain barrier.

In a forthcoming chemical journal article, Meinwald and his coworkers will describe both the structure and synthesis of the new chemical in detail. The original characterization and synthesis of HF-7 were done at Cornell by graduate students Kevin and Jinping McCormick, and elaborated by Yingbo Li, a graduate student, and Bruce Ganem, Cornell professor of chemistry. Professor Jacques H. van Boom at Lieden University and his Dutch research team of Howard I. Dunstee, Anke K. van Engen, and Gijs van de Marel, developed a new and improved synthesis of this novel natural product.


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