Irreversible inhibition of BoNT/A protease: proximity-driven reactivity contingent upon a bifunctional approach

• Published in: MedChemComm Vol. 12; no. 6; pp. 96 - 969
• Main Authors: Turner, Lewis D, Nielsen, Alexander L, Lin, Lucy, Pellett, Sabine, Sugane, Takashi, Olson, Margaret E, Johnson, Eric A, Janda, Kim D
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 23.06.2021; RSC
• Subjects: Ablation; Bioterrorism; Botulinum toxin type A; Botulism; Chemistry; Covalent bonds; Evaluation; Food contamination; Glutathione; High-performance liquid chromatography; Hydroxamic acid; Inhibition; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Matrix metalloproteinase; Matrix metalloproteinases; Muscles; Neurotoxins; NMR; Nuclear magnetic resonance; Paralysis; Selectivity; Time dependence; Toxicity; Toxins; Warheads; Zinc

Botulinum neurotoxin A (BoNT/A) is categorized as a Tier 1 bioterrorism agent and persists within muscle neurons for months, causing paralysis. A readily available treatment that abrogates BoNT/A's toxicity and longevity is a necessity in the event of a widespread BoNT/A attack and for clinical...