The strange case of the botulinum neurotoxin: using chemistry and biology to modulate the most deadly poison.
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.
Willis
Bert
B
Department of Chemistry, Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Eubanks
Lisa M
LM
Dickerson
Tobin J
TJ
Janda
Kim D
KD
D001428:Bacterial Vaccines / Q000737:chemistry / Q000627:therapeutic use; D001905:Botulinum Toxins / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000633:toxicity; D001906:Botulism / Q000188:drug therapy* / Q000517:prevention & control; D015195:Drug Design; D006801:Humans; D018716:Molecular Mimicry; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use; D009435:Synaptic Transmission / Q000187:drug effects
D001428:Bacterial Vaccines; D010455:Peptides; D001905:Botulinum Toxins