title: Picolinic acids as β-exosite inhibitors of botulinum neurotoxin A light chain.
abstract: In developing small-molecule inhibitors of botulinum neurotoxin serotype A light chain (BoNT/A LC), substituted picolinic acids were identified. Extensive investigation into the SAR of the picolinic acid scaffold revealed 5-(1-butyl-4-chloro-1H-indol-2-yl)picolinic acid (CBIP), which possessed low micromolar activity against BoNT/A. Kinetic and docking studies demonstrated binding of CBIP to the β-exosite: a largely unexplored site on the LC that holds therapeutic relevance for botulism treatment.
authors.affiliation: Departments of Chemistry, Immunology and Microbial Sciences, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA. kdjanda@scripps.edu.
authors.forename: Paul T
authors.identifier: http://orcid.org/0000-0002-8357-1743
authors.initials: PT
authors.lastname: Bremer
authors.affiliation: Departments of Chemistry, Immunology and Microbial Sciences, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA. kdjanda@scripps.edu.
authors.forename: Song
authors.initials: S
authors.lastname: Xue
authors.affiliation: Departments of Chemistry, Immunology and Microbial Sciences, Worm Institute for Research and Medicine (WIRM), The Scripps Research Institute, 10550 N. Torrey Pines Rd, La Jolla, CA 92037, USA. kdjanda@scripps.edu.
authors.forename: Kim D
authors.initials: KD
authors.lastname: Janda
mesh_terms: D019274:Botulinum Toxins, Type A / Q000037:antagonists & inhibitors*; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology*; D010848:Picolinic Acids / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology*
chemical_list: D007502:Iron Chelating Agents; D010848:Picolinic Acids; D011480:Protease Inhibitors; D019274:Botulinum Toxins, Type A; C030614:picolinic acid