Synthesis and Evaluation of Compound 35 as a Potential Botulinum Neurotoxin Inhibitor
Abstract
A pseudotripeptide inhibitor designated as compound 35 was synthesized and tested for its ability to inhibit the catalytic activity of botulinum neurotoxin serotype A (BoNT/A) or serotype B (BoNT/B). Catalytic activity was assessed using a fluorescent microplate assay in which an immobilized substrate for BoNT/A (SNAP-25 peptide) or BoNT/B (synaptobrevin peptide) was released into the medium following addition of the appropriate BoNT light chain (LC). Compound 35 was able to inhibit both LCs with an IC50 of 1 micro M for BoNT/A and 7 micro M for BoNT/B. Compound 35 is the first inhibitor that has been found to be effective against two serotypes of BoNT; these two serotypes are responsible for most human intoxications.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 31, 2020
- Accession Number
- AD1108968
Entities
People
- Andrew Ternay
- Heidi Hoard-fruchey
- James Nicholson
- Michael Adler
Organizations
- United States Army Medical Research Institute of Chemical Defense
- University of Denver