Combinatorial Strategies and High Throughput Screening in Drug Discovery Targeted to Channel of Botulinum
Abstract
This program examines innovative approaches and powerful new technologies to identify selective and potent agents directed to prevent or relieve the neuroparalytic toxic actions of botulinum toxin A (BoNTA)1. The focus is on the ion channel forming activity pf BoNTs as a validated target to screen for inhibitors of the translocation of the light chain into the cytosol and therefore to attenuate the BoNT neurotoxicity. The key of the program is based on our discovery that the heavy chain (HC) of BoNT acts as both a channel and a transmembrane chaperone for the light chain (LC) to ensure a trans location competent conformation during its transit from the acidic endosome into the cytosol - its site of action. This is an exciting time to focus on innovative technologies to uncover lead compounds that may represent a potential new generation of useful and safe antidotes for BoNTs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2004
- Accession Number
- ADA428643
Entities
People
- Mauricio Montel
Organizations
- University of California, San Diego