title: Paclitaxel is an inhibitor and its boron dipyrromethene derivative is a fluorescent recognition agent for botulinum neurotoxin subtype A.
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.
authors.affiliation: Department of Chemistry, Lakehead University and Thunder Bay Regional Research Institute, Thunder Bay, Ontario P7B 5E1, Canada.
authors.forename: Saedeh
authors.initials: S
authors.lastname: Dadgar
authors.forename: Zack
authors.initials: Z
authors.lastname: Ramjan
authors.forename: Wely B
authors.initials: WB
authors.lastname: Floriano
mesh_terms: D001896:Boron Compounds / Q000737:chemistry*; D019274:Botulinum Toxins, Type A / Q000032:analysis*; D031541:Fluorescence Resonance Energy Transfer; D008024:Ligands; D008958:Models, Molecular; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001896:Boron Compounds; D008024:Ligands; D019274:Botulinum Toxins, Type A; D017239:Paclitaxel