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      Paclitaxel is an inhibitor and its boron dipyrromethene derivative is a fluorescent recognition agent for botulinum neurotoxin subtype A.

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          Abstract

          We have successfully identified one new inhibitor and one new fluorescent recognition agent for the botulinum neurotoxin subtype A (BoNT/A) using the virtual screening protocol "protein scanning with virtual ligand screening" (PSVLS). Hit selection used an in-house developed holistic binding scoring method. Selected hits were tested experimentally for inhibitory activity using fluorescence resonance energy transfer (FRET) assays against the light chain (catalytic domain) of BoNT/A. Ligand binding was determined against the light and heavy chain BoNT/A complex through either radiolabeled ligand binding assays (nonfluorescent ligands) or fluorescence intensity assays (fluorescent ligands). These experimental assays have confirmed one compound (paclitaxel) to inhibit BoNT/A's proteolytic activity experimentally with an IC50 of 5.2 μM. A fluorescent derivative was also confirmed to bind to the toxin and therefore is a suitable candidate for the rational design of new detection agents and for the development of fluorescence-based multiprobe detection assays.

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          Author and article information

          Journal
          J. Med. Chem.
          Journal of medicinal chemistry
          American Chemical Society (ACS)
          1520-4804
          0022-2623
          Apr 11 2013
          : 56
          : 7
          Affiliations
          [1 ] Department of Chemistry, Lakehead University and Thunder Bay Regional Research Institute, Thunder Bay, Ontario P7B 5E1, Canada.
          NIHMS459119
          10.1021/jm301829h
          3670186
          23484537

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