Abstract
Biological toxins, which are produced by microorganisms, plants, or animals, cause serious illnesses in humans. Some of these toxins, for example, botulinum neurotoxin, are potential agents of biological warfare and are also increasingly being used for therapeutic and cosmetic purposes. Despite the potential damage they could cause to human health, no drugs are currently available for post-intoxication therapy. Recent progress in drug discovery efforts for botulinum neurotoxins and unmet challenges are discussed. Aided with the crystal structures of apo- and cognate substrate-bound catalytic domain, a number of peptide and small-molecule non-peptide inhibitors have been identified for various serotypes, and pharmacophore models are emerging. But there is limited success in translating these inhibitors into active compounds in cellular assays and in vivo models. Factors such as the unusually large surface area of the toxin-substrate interaction interface, the flexible loops lining the active site, involvement of a metal ion in the catalytic activity, and molten globule form of the enzyme at physiological temperature contribute to this challenge and are discussed.
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Kumar, G. (2015). Challenges in Developing Biotoxin Inhibitors. In: Gopalakrishnakone, P., Balali-Mood, M., Llewellyn, L., Singh, B.R. (eds) Biological Toxins and Bioterrorism. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5869-8_27
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DOI: https://doi.org/10.1007/978-94-007-5869-8_27
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