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Scientists develop a way to make the deadliest toxin known even more toxic

According to the study, the molecules bind to specific sites on the neurotoxin protein, increasing protease activity and enhancing the toxin's effect. In some cases, the study noted, the activation power of the new molecules was as much as fourteen-fold, the greatest increase in activation ever reported for a protease; before this study, a two-fold activation of a protease was referred to as a state of "superactivation." Proteases are enzymes that act as cellular catalysts, breaking up proteins into smaller elements such as amino acids and reducing the amount of energy needed for the activation.

The study was released in an advanced online version by the Journal of the American Chemical Society.

Kim Janda, currently the Ely R. Callaway Jr. professor of chemistry, director of the Worm Institute for Research and Medicine (WIRM), and head of the laboratory that conducted the study, said, "Since the botulinum neurotoxin is the most poisonous toxin known, finding a compound to activate it might seem somewhat counterproductive. But the range of clinical uses for the toxin have increased well beyond its cosmetic use--multiple sclerosis, stroke, cerebral palsy, migraine, and backache are just a few of the conditions for which BoNT has proven surprisingly effective. The discovery of small molecule activators may ultimately provide a valuable method for minimizing dosage, reducing resistance, and increasing its clinical efficacy."

Botulinum neurotoxins are the most lethal poisons known. They produce progressive paralysis by binding to nerves at the point where they connect to muscles, and blocking the release of acetylcholine, which signals the muscles to contract, including those that regulate breathing. Blocking the nerve signal results in paralysis and, unless treated quickly, death. A lethal dose is small--eight tenths of an inhaled microgram for a 175-pound person.

Because of its highly potent neurotoxic activity, Janda added, the use of
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Source:Scripps Research Institute


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