A cross-over inhibitor of the botulinum neurotoxin light chain B: a natural product implicating an exosite mechanism of action

Chem Commun (Camb). 2011 Feb 14;47(6):1713-5. doi: 10.1039/c0cc04078a. Epub 2011 Jan 4.

Abstract

Clostridium botulinum produces the most lethal toxins known to man, as such they are high risk terrorist threats, and alarmingly there is no approved therapeutic. We report the first cross-over small molecule inhibitor of these neurotoxins and propose a mechanism by which it may impart its inhibitory activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Biological Products / pharmacology*
  • Biological Products / therapeutic use
  • Botulinum Toxins / antagonists & inhibitors*
  • Botulinum Toxins / chemistry
  • Botulinum Toxins / metabolism
  • Caffeic Acids / pharmacology
  • Caffeic Acids / therapeutic use*
  • Catalytic Domain
  • Clostridium botulinum / metabolism*
  • Cross-Linking Reagents / chemistry
  • Fluorescence Resonance Energy Transfer
  • HIV Integrase Inhibitors / pharmacology
  • HIV Integrase Inhibitors / therapeutic use*
  • Humans
  • Male
  • Molecular Sequence Data
  • Neurotoxins / antagonists & inhibitors*
  • Neurotoxins / chemistry
  • Neurotoxins / metabolism
  • Substrate Specificity
  • Succinates / pharmacology
  • Succinates / therapeutic use*
  • Synaptosomal-Associated Protein 25 / antagonists & inhibitors
  • Synaptosomal-Associated Protein 25 / chemistry
  • Synaptosomal-Associated Protein 25 / metabolism
  • Vesicle-Associated Membrane Protein 2 / antagonists & inhibitors
  • Vesicle-Associated Membrane Protein 2 / chemistry
  • Vesicle-Associated Membrane Protein 2 / metabolism

Substances

  • Biological Products
  • Caffeic Acids
  • Cross-Linking Reagents
  • HIV Integrase Inhibitors
  • Neurotoxins
  • Succinates
  • Synaptosomal-Associated Protein 25
  • Vesicle-Associated Membrane Protein 2
  • Botulinum Toxins
  • chicoric acid