Combinatorial Strategies and High Throughput Screening in Drug Discovery Targeted to the Channel of Botulinum Neurotoxin
Abstract
The ultimate goal of this program is to discover selective and potent drugs targeted to prevent or relieve the neurotoxic actions of botulinum neurotoxin (BoNT) A. A major goal of this program is the identification of open channel blockers as a single class of drugs that would be effective against all BoNT isoforms. We consider the BoNT channel as a validated target for intervention aimed to inhibit the translocation of the light chain into the cytosol and therefore to attenuate the BoNT neurotoxicity. The major focus thus far has been the implementation of a reliable and robust high-throughput screen for blockers specific for BoNT using Neuro 2A cells in which BoNTA forms channels with similar properties to those previously characterized in lipid bilayers. The immediate task during the present reporting period involved the detailed characterization of the channel and chaperone activity of BoNTA on Neuro2A cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2006
- Accession Number
- ADA471426
Entities
People
- Mauricio Montal
Organizations
- University of California, San Diego