Review
The Strange Case of the Botulinum Neurotoxin: Using Chemistry and Biology to Modulate the Most Deadly Poison
Bert Willis Dr.,
Lisa M. Eubanks Dr.,
Tobin J. Dickerson Prof. Dr.,
Kim D. Janda Prof. Dr.,
Bert Willis Dr.
Departments of Chemistry and Immunology, Skaggs Institute for Chemical Biology, and Worm Institute of Research & Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-2595
Search for more papers by this authorLisa M. Eubanks Dr.
Departments of Chemistry and Immunology, Skaggs Institute for Chemical Biology, and Worm Institute of Research & Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-2595
Search for more papers by this authorTobin J. Dickerson Prof. Dr.
Departments of Chemistry and Immunology, Skaggs Institute for Chemical Biology, and Worm Institute of Research & Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-2595
Search for more papers by this authorKim D. Janda Prof. Dr.
Departments of Chemistry and Immunology, Skaggs Institute for Chemical Biology, and Worm Institute of Research & Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-2595
Search for more papers by this authorBert Willis Dr.,
Lisa M. Eubanks Dr.,
Tobin J. Dickerson Prof. Dr.,
Kim D. Janda Prof. Dr.,
Bert Willis Dr.
Departments of Chemistry and Immunology, Skaggs Institute for Chemical Biology, and Worm Institute of Research & Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-2595
Search for more papers by this authorLisa M. Eubanks Dr.
Departments of Chemistry and Immunology, Skaggs Institute for Chemical Biology, and Worm Institute of Research & Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-2595
Search for more papers by this authorTobin J. Dickerson Prof. Dr.
Departments of Chemistry and Immunology, Skaggs Institute for Chemical Biology, and Worm Institute of Research & Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-2595
Search for more papers by this authorKim D. Janda Prof. Dr.
Departments of Chemistry and Immunology, Skaggs Institute for Chemical Biology, and Worm Institute of Research & Medicine (WIRM), The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA), Fax: (+1) 858-784-2595
Search for more papers by this authorGraphical Abstract
Two sides to the story: Botulinum neurotoxin is among the most lethal species known to man, yet has profound clinical utility. Through the combination of recent structural, biochemical, and biophysical studies, new insights into toxin action have been achieved, leading to a range of small molecules, peptides, and antibodies for treating botulism.
Abstract
In the classic novella “The Strange Case of Dr. Jekyll and Mr. Hyde”, Robert Louis Stevenson paints a stark picture of the duality of good and evil within a single man. Botulinum neurotoxin (BoNT), the most potent known toxin, possesses an analogous dichotomous nature: It shows a pronounced morbidity and mortality, but it is used with great effect in much lower doses in a wide range of clinical scenarios. Recently, tremendous strides have been made in the basic understanding of the structure and function of BoNT, which have translated into widespread efforts towards the discovery of biomacromolecules and small molecules that specifically modulate BoNT activity. Particular emphasis has been placed on the identification of inhibitors that can counteract BoNT exposure in the event of a bioterrorist attack. This Review summarizes the current advances in the development of therapeutics, including vaccines, peptides, and small-molecule inhibitors, for the prevention and treatment of botulism.
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