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Picolinic acids as ?-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 ?-exosite: a largely unexplored site on the LC that holds therapeutic relevance for botulism treatment.

SUBMITTER: Bremer PT

PROVIDER: S-EPMC5085802 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Picolinic acids as β-exosite inhibitors of botulinum neurotoxin A light chain.

Bremer Paul T PT Xue Song S Janda Kim D KD

Chemical communications (Cambridge, England) 20161001 84

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 treatmen ...[more]

PMID: 27722252

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