Work

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

Year: 2016

Type: article

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.

Source: Chemical Communications

DOI: 10.1039/c6cc06749b

Authors: Paul T. Bremer, Song Xue, Kim D. Janda

Institution: Scripps Research Institute

Language: English

Topic: Botulinum Toxin and Related Neurological Disorders

Subfield: Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institute of Allergy and Infectious Diseases